• Search Menu
  • Advance articles
  • Editor's Choice
  • Supplement Archive
  • Cover Archive
  • IDSA Journals
  • Clinical Infectious Diseases
  • Open Forum Infectious Diseases
  • Author Guidelines
  • Open Access
  • Why Publish
  • Advertising and Corporate Services
  • Advertising
  • Reprints and ePrints
  • Sponsored Supplements
  • Branded Books
  • Journals Career Network
  • About The Journal of Infectious Diseases
  • About the Infectious Diseases Society of America
  • About the HIV Medicine Association
  • IDSA COI Policy
  • Editorial Board
  • Self-Archiving Policy
  • For Reviewers
  • For Press Offices
  • Journals on Oxford Academic
  • Books on Oxford Academic

Issue Cover

Article Contents

Conclusions.

  • < Previous

The Extended Impact of Human Immunodeficiency Virus/AIDS Research

  • Article contents
  • Figures & tables
  • Supplementary Data

Tara A Schwetz, Anthony S Fauci, The Extended Impact of Human Immunodeficiency Virus/AIDS Research, The Journal of Infectious Diseases , Volume 219, Issue 1, 1 January 2019, Pages 6–9, https://doi.org/10.1093/infdis/jiy441

  • Permissions Icon Permissions

Human immunodeficiency virus (HIV) is one of the most extensively studied viruses in history, and numerous extraordinary scientific advances, including an in-depth understanding of viral biology, pathogenesis, and life-saving antiretroviral therapies, have resulted from investments in HIV/AIDS research. While the substantial investments in HIV/AIDS research are validated solely on these advances, the collateral broader scientific progress resulting from the support of HIV/AIDS research over the past 30 years is extraordinary as well. The positive impact has ranged from innovations in basic immunology and structural biology to treatments for immune-mediated diseases and cancer and has had an enormous effect on the research and public and global health communities well beyond the field of HIV/AIDS. This article highlights a few select examples of the unanticipated and substantial positive spin-offs of HIV/AIDS research on other scientific areas.

The first cases of AIDS were reported in the United States 37 years ago. Since then, >77 million people have been infected worldwide, resulting in over 35 million deaths. Currently, there are 36.9 million people living with human immunodeficiency virus (HIV), 1.8 million new infections, and nearly 1 million AIDS-related deaths annually [ 1 ]. Billions of research dollars have been invested toward understanding, treating, and preventing HIV infection. The largest funder of HIV/AIDS research is the National Institutes of Health (NIH), investing nearly $69 billion in AIDS research from fiscal years 1982–2018. Despite the staggering disease burden, the scientific advances directly resulting from investments in AIDS research have been extraordinary. HIV is one of the most intensively studied viruses in history, leading to an in-depth understanding of viral biology and pathogenesis. However, the most impressive advances in HIV/AIDS research have come in the arena of antiretroviral therapy. Before the development of these life-saving drugs, AIDS was an almost universally fatal disease. Since the demonstration in 1987 that a single drug, zidovudine, better known as azidothymidine or AZT, could partially and temporarily suppress virus replication [ 2 ], the lives of people living with HIV have been transformed by the current availability of >30 antiretroviral drugs that, when administered in combinations of 3 drugs, now in a single daily pill, suppress the virus to undetectable levels. Today, if a person in their 20s is infected and given a combination of antiretroviral drugs that almost invariably will durably suppress virus to below detectable levels, they can anticipate living an additional 50 years, allowing them almost a normal life expectancy [ 3 ]. In addition, a person receiving antiretroviral therapy with an undetectable viral load will not transmit virus to their uninfected sexual partner. This strategy is referred to as “treatment as prevention” [ 4 ]. Also, administration of a single pill containing 2 antiretroviral drugs taken daily by an at-risk uninfected person decreases the chance of acquiring HIV by >95%. Finally, major strides are being made in the quest for a safe and effective HIV vaccine [ 5 ].

The enormous investment in HIV research is clearly justified and validated purely on the basis of advances specifically related to HIV/AIDS. However, the collateral advantages of this investment above and beyond HIV/AIDS have been profound, leading to insights and concrete advances in separate, diverse, and unrelated fields of biomedical research and medicine. In the current Perspective, we discuss a few select examples of the positive spin-offs of HIV/AIDS research on other scientific areas ( Table 1 ).

Positive Spin-offs of Human Immuno deficiency Virus/AIDS Research on Other Areas of Medicine

Abbreviation: HIV, human immunodeficiency virus.

Regulation of the Human Immune System

Congenital immunodeficiencies have been described as “experiments of nature,” whereby a specific defect in a single component of the complex immune system sheds light on the entire system. Such is the case with AIDS, an acquired defect in the immune system whereby HIV specifically and selectively infects and destroys the CD4 + subset of T lymphocytes [ 6 ]. In this respect, HIV infection functions as a natural experiment that elucidates the complexity of the human immune system. The selectivity of this defect and its resulting catastrophic effect on host defense mechanisms, as manifested by the wide range of opportunistic infections and neoplasms, underscore the critical role this cell type plays in the overall regulation of the human immune system. This has provided substantial insights into the pathogenesis of an array of other diseases characterized by aberrancies of immune regulation. Additionally, the in-depth study of immune dysfunction in HIV disease has shed light on the role of the immune system in surveillance against a variety of neoplastic diseases, such as non-Hodgkin lymphoma and Kaposi sarcoma. As a result of its association with HIV/AIDS, Kaposi sarcoma was discovered to be caused by human herpesvirus 8 [ 7 ].

Targeted Antiviral Drug Development

Targeted antiviral drug development did not begin with HIV infection. However, the enormous investments in biomedical research supported by the NIH and in drug development supported by pharmaceutical companies led to highly effective antiretroviral drugs targeting the enzymes reverse transcriptase, protease, and integrase, among other vulnerable points in the HIV replication cycle, and have transformed the field of targeted drug development, bringing it to an unprecedented level of sophistication. Building on 3 decades of experience, this HIV model has been applied in the successful development of antiviral drugs for other viral diseases, including the highly effective and curative direct-acting antivirals for hepatitis C [ 8 ].

Probing the B-Cell Repertoire

The past decade has witnessed extraordinary advances in probing the human B-cell lineage resulting from the availability of highly sophisticated technologies in cellular cloning and genomic sequencing [ 9 ]. AIDS research aimed at developing broadly reactive neutralizing antibodies against HIV and an HIV vaccine that could induce broadly neutralizing antibodies has greatly advanced the field of interrogation of human B-cell lineages, leading to greater insights into the humoral response to other infectious diseases, including Ebola [ 10 ], Zika [ 11 ], and influenza [ 12 ], as well as a range of autoimmune, neoplastic, and other noncommunicable diseases [ 13 ].

Structure-Based Vaccine Design

Although a safe and effective HIV vaccine has not yet been developed, the discipline of structure-based vaccine design using protein X-ray crystallography and cryoelectron microscopy has matured greatly in the context of HIV vaccine research. The design of immunogens based on the precise conformation of epitopes in the viral envelope as they bind to neutralizing antibodies has been perfected within the arena of HIV vaccine immunogen design. This has had immediate positive spinoffs in the design of vaccines for other viruses, such as respiratory syncytial virus, in which the prefusion glycoprotein was identified as the important immunogen for a vaccine using structure-based approaches [ 14 ].

Advances in HIV/AIDS-Related Technologies

Insights into the basic immunology of HIV drove the development and optimization of several broadly applicable technologies. Using inactivated HIV as a means of altering T lymphocytes to modulate the immune response, safe lentiviral gene therapy vectors are now US Food and Drug Administration–approved to treat certain cancers (eg, acute lymphoblastic leukemia) [ 15 ]. Additionally, it was discovered early in the epidemic that HIV is associated with the loss of CD4 + T lymphocytes [ 16 ]. While much of the initial research on CD4 + T lymphocytes was possible due to existing flow cytometry technologies, probing the complexities of immune dysregulation in HIV infection spurred the development of multicolor cytofluorometric technologies that have proven extremely useful for studying a variety of other diseases characterized by immune dysfunction [ 17 ]. The reality of utilizing these technologies in resource-poor areas accelerated the advancement of new simplified, automated, affordable, and portable point-of-care devices with broader implications for clinical medicine [ 18 ].

Role of Immune Activation in Disease Pathogenesis

Studying the pathogenesis of HIV disease has clearly demonstrated that aberrant immune activation stimulated by virus replication is the driving force of HIV replication [ 19 ]. In essence, the somewhat paradoxical situation exists whereby the very immune activation triggered by the virus in an attempt to control virus replication creates the microenvironment where the virus efficiently replicates. Even when the virus is effectively suppressed by antiretroviral drugs, a low degree of immune activation persists [ 20 ]. In this regard, the flagrant immune activation associated with uncontrolled virus replication, as well as the subtle immune activation associated with control of virus replication, are important pathogenic triggers of the increased cardiovascular and other organ system diseases associated with HIV infection. This direct association of even subtle levels of immune activation seen in HIV infection with a variety of systemic diseases has led to considerable insight into the role of immune activation and inflammation in human disease [ 21 ]. For example, recognition of the increased incidence of heart disease in the HIV population that is associated with chronic inflammation has stimulated interdisciplinary advances in understanding and treating coronary heart disease apart from HIV infection [ 22 ].

Comorbidities in HIV Disease

Antiretroviral therapy, which has transformed HIV treatment, is shifting the incidence of certain diseases in people living with HIV. Even when well-controlled by antiretrovirals, HIV disease is associated with an increased incidence of diseases, such as cardiovascular disease, kidney and liver disease, the premature appearance of pathophysiologic processes associated with aging, and several cancers [ 21–24 ]. This is especially true for non-AIDS-defining cancers, whose incidence rates are increasing while AIDS-defining cancer rates are decreasing [ 24 ]. In lower-income countries, tuberculosis is a common coinfection with HIV, and HIV coinfection was shown to be a key risk factor for progression of latent Mycobacterium tuberculosis infection to active disease [ 25 ]. There are a variety of ongoing studies [ 21 ] investigating the pathogenic bases of these conditions to shed greater insight into their causes and potential interventions that might impact these diseases apart from HIV infection and immunodeficiency.

The collateral advantages resulting from the substantial resources devoted to HIV/AIDS research over the past 30 years are extraordinary. From innovations in basic immunology and structural biology to treatments for immune-mediated diseases and cancer, the conceptual and technological advances resulting from HIV/AIDS research have had an enormous impact on the research and public and global health communities over and above the field of HIV/AIDS. The HIV/AIDS research model has proven that cross-fertilization of ideas, innovation, and research progress can lead to unforeseen and substantial advantages for a variety of other diseases.

Acknowledgments.  The authors thank Carl Dieffenbach, Daniel Rotrosen, Charles Hackett, and Robert Eisinger for their helpful input in preparation of the manuscript.

Potential conflicts of interest.  Both authors: No reported conflicts of interest. Both authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Joint United Nations Progamme on HIV/AIDS . Fact sheet: latest statistics on the status of the AIDS epidemic . http://www.unaids.org/en/resources/fact-sheet . Accessed 23 July 2018.

Fischl MA , Richman DD , Grieco MH , et al.    The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial . N Engl J Med   1987 ; 317 : 185 – 91 .

Google Scholar

Samji H , Cescon A , Hogg RS , et al.    North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) of IeDEA . Closing the gap: increases in life expectancy among treated HIV-positive individuals in the United States and Canada . PLoS One   2013 ; 8 : e81355 .

Lundgren JD , Babiker AG , Gordin F , et al.    INSIGHT START Study Group . Initiation of antiretroviral therapy in early asymptomatic HIV infection . N Engl J Med   2015 ; 373 : 795 – 807 .

Trovato M , D’Apice L , Prisco A , De Berardinis P . HIV vaccination: a roadmap among advancements and concerns . Int J Mol Sci   2018 ; 19 . doi: 10.3390/ijms19041241 .

Dalgleish AG , Beverley PC , Clapham PR , Crawford DH , Greaves MF , Weiss RA . The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus . Nature   1984 ; 312 : 763 – 7 .

Schulz TF , Boshoff CH , Weiss RA . HIV infection and neoplasia . Lancet   1996 ; 348 : 587 – 91 .

Wyles DL . Antiviral resistance and the future landscape of hepatitis C virus infection therapy . J Infect Dis   2013 ; 207 ( Suppl 1 ): S33 – 9 .

Boyd SD , Crowe JE Jr . Deep sequencing and human antibody repertoire analysis . Curr Opin Immunol   2016 ; 40 : 103 – 9 .

Flyak AI , Kuzmina N , Murin CD , et al.    Broadly neutralizing antibodies from human survivors target a conserved site in the Ebola virus glycoprotein HR2-MPER region . Nat Microbiol   2018 ; 3 : 670 – 7 .

Sapparapu G , Fernandez E , Kose N , et al.    Neutralizing human antibodies prevent Zika virus replication and fetal disease in mice . Nature   2016 ; 540 : 443 – 7 .

Raymond DD , Bajic G , Ferdman J , et al.    Conserved epitope on influenza-virus hemagglutinin head defined by a vaccine-induced antibody . Proc Natl Acad Sci U S A   2018 ; 115 : 168 – 73 .

Röhn TA , Bachmann MF . Vaccines against non-communicable diseases . Curr Opin Immunol   2010 ; 22 : 391 – 6 .

Tian D , Battles MB , Moin SM , et al.    Structural basis of respiratory syncytial virus subtype-dependent neutralization by an antibody targeting the fusion glycoprotein . Nat Commun   2017 ; 8 : 1877 .

US Food and Drug Administration . FDA approval brings first gene therapy to the United States . Silver Spring, MD : FDA , 2017 .

Google Preview

Gottlieb MS , Schroff R , Schanker HM , et al.    Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiency . N Engl J Med   1981 ; 305 : 1425 – 31 .

Chattopadhyay PK , Roederer M . Cytometry: today’s technology and tomorrow’s horizons . Methods   2012 ; 57 : 251 – 8 .

Kestens L , Mandy F . Thirty-five years of CD4 T-cell counting in HIV infection: from flow cytometry in the lab to point-of-care testing in the field . Cytometry B Clin Cytom   2017 ; 92 : 437 – 44 .

Moir S , Fauci AS . B-cell exhaustion in HIV infection: the role of immune activation . Curr Opin HIV AIDS   2014 ; 9 : 472 – 7 .

Paiardini M , Müller-Trutwin M . HIV-associated chronic immune activation . Immunol Rev   2013 ; 254 : 78 – 101 .

Lucas S , Nelson AM . HIV and the spectrum of human disease . J Pathol   2015 ; 235 : 229 – 41 .

Boccara F , Lang S , Meuleman C , et al.    HIV and coronary heart disease: time for a better understanding . J Am Coll Cardiol   2013 ; 61 : 511 – 23 .

Torres RA , Lewis W . Aging and HIV/AIDS: pathogenetic role of therapeutic side effects . Lab Invest   2014 ; 94 : 120 – 8 .

Thrift AP , Chiao EY . Are non-HIV malignancies increased in the HIV-infected population ? Curr Infect Dis Rep   2018 ; 20 : 22 .

Getahun H , Gunneberg C , Granich R , Nunn P . HIV infection-associated tuberculosis: the epidemiology and the response . Clin Infect Dis   2010 ; 50 ( Suppl 3 ): S201 – 7 .

  • acquired immunodeficiency syndrome

Email alerts

Related articles in pubmed, citing articles via, looking for your next opportunity.

  • Recommend to your Library

Affiliations

  • Online ISSN 1537-6613
  • Print ISSN 0022-1899
  • Copyright © 2024 Infectious Diseases Society of America
  • About Oxford Academic
  • Publish journals with us
  • University press partners
  • What we publish
  • New features  
  • Open access
  • Institutional account management
  • Rights and permissions
  • Get help with access
  • Accessibility
  • Media enquiries
  • Oxford University Press
  • Oxford Languages
  • University of Oxford

Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide

  • Copyright © 2024 Oxford University Press
  • Cookie settings
  • Cookie policy
  • Privacy policy
  • Legal notice

This Feature Is Available To Subscribers Only

Sign In or Create an Account

This PDF is available to Subscribers Only

For full access to this pdf, sign in to an existing account, or purchase an annual subscription.

Volume 27, Number 6—June 2021

Perspective

Reflections on 40 years of aids.

Cite This Article

June 2021 marks the 40th anniversary of the first description of AIDS. On the 30th anniversary, we defined priorities as improving use of existing interventions, clarifying optimal use of HIV testing and antiretroviral therapy for prevention and treatment, continuing research, and ensuring sustainability of the response. Despite scientific and programmatic progress, the end of AIDS is not in sight. Other major epidemics over the past decade have included Ebola, arbovirus infections, and coronavirus disease (COVID-19). A benchmark against which to compare other global interventions is the HIV/AIDS response in terms of funding, coordination, and solidarity. Lessons from Ebola and HIV/AIDS are pertinent to the COVID-19 response. The fifth decade of AIDS will have to position HIV/AIDS in the context of enhanced preparedness and capacity to respond to other potential pandemics and transnational health threats.

“When the history of AIDS and the global response is written, our most precious contribution may well be that, at a time of plague, we did not flee, we did not hide, we did not separate ourselves.”

—Jonathan Mann, Founding Director of Project SIDA and the World Health Organization Global Programme on AIDS, 1998

Forty years ago, on June 5, 1981, the Centers for Disease Control’s Morbidity and Mortality Weekly Report described 5 cases of Pneumocystis pneumonia in gay men ( 1 ). That report heralded the HIV/AIDS pandemic, which has resulted in over 75 million HIV infections and 32 million deaths. In 2011, we reviewed 30 years of AIDS and commented that the HIV/AIDS response would be a benchmark against which responses to other health threats would be compared ( 2 ). After 40 years of AIDS, we present our personal reflections on scientific and global health evolution over the fourth decade of AIDS in a world that has recently suffered other major epidemics. We focus on biomedical advances because these have had the greatest effect on HIV transmission and disease; advances in structural and behavioral interventions are reviewed in the CDC Compendium of Evidence-Based Interventions and Best Practices for HIV Prevention ( 3 ).

After the initial MMWR report was published, it took 2–3 years for the cause of AIDS, the novel retrovirus designated HIV, to be identified ( 4 , 5 ), and many more years to uncover its simian origin ( 6 ). Because of the asymptomatic spread of HIV, the long incubation period before disease, and transmission through sex and blood, millions of persons around the world, including several hundred thousand in the United States, were infected by the time the first AIDS cases were reported. The epidemiology and natural history of HIV infection, combining elements of acute and chronic diseases, ensured a diverse and long-lasting pandemic.

The history of HIV/AIDS and the struggle to contain it have seen the best and worst of human nature. Frequent examples of discrimination and exclusion are contrasted by leadership, illustrated by community activists ( 7 ), Jonathan Mann molding the first global response ( 8 ), Kofi Annan rallying the United Nations behind the search for a global fund ( 9 ), and President George W. Bush committing United States generosity to a war on HIV/AIDS of uncertain duration ( 10 ). Despite continued instances of injustice, the story has overall been a positive one, providing lessons for how to respond to other epidemic and pandemic threats.

Evolving Epidemiology

The Joint United Nations Programme on HIV/AIDS (UNAIDS) estimates that in 2019, 38 million persons worldwide were living with HIV, 1.7 million became newly infected, and 690,000 died with HIV disease ( 11 ). Compared with 2010 estimates, overall HIV incidence in 2019 decreased by 23% and mortality by 37%. However, age stratification shows that new infections have decreased by 52% among children but by only 13% among adults. With reduced mortality rates yet continued HIV incidence and population growth, the overall number of persons living with HIV was 24% greater in 2019 than in 2010.

Global summaries hide regional differences. The epicenter of the pandemic remains in East and southern Africa, which account for 54% of all HIV-infected persons and 43% of incident HIV infections and deaths ( 11 ). High prevalence of HIV-infected persons with unsuppressed viremia predicts high incidence and maintenance of community infection, an observation that applies to regions and countries, as well as specific populations such as men who have sex with men (MSM).

The next greatest HIV burden is in the Asia and Pacific region, where the population is vastly greater than that of East and southern Africa but there are 3.5 times fewer HIV-infected persons ( 11 ). Despite overall prevention progress, HIV incidence has not declined equally everywhere; little success has been seen in eastern Europe, the Middle East, and Central Asia.

Ever clearer is the global burden of HIV in key populations: MSM, transgender persons, people who inject drugs, sex workers and their clients, and incarcerated persons. In 2019, an estimated 62% of all new HIV infections were in members of those key populations ( 11 ). In 7 of the 8 UNAIDS regions, key populations accounted for 60%–99% of incident HIV infections; only in East and southern Africa, where the proportion was 28%, were new infections predominant in general populations ( 11 ).

Among high-income nations, the most heavily affected country is still the United States. In 2018, a total of 37,881 HIV infections were newly reported, with regional differences ( 12 ). In the South, the rate of new infections was more than twice that for the Midwest, where the rate was the lowest. Major disparities by race/ethnicity persist; the rate among Black/African American persons is 2 times that among Hispanic and 8 times that among White persons. Also associated with higher rates are factors indicating social deprivation and poverty, even allowing for racial and ethnic disparities. Among new HIV infections, 70% resulted from male-to-male sex. A cause for concern is potential overlap between the HIV/AIDS and opioid epidemics through increased drug injection and needle sharing, which has resulted in explosive HIV outbreaks ( 13 ).

Evolving Science and Program

In our 2011 commentary ( 2 ), we considered the following as priorities: improving use of existing interventions, defining how best to use HIV testing and antiretroviral therapy (ART) for prevention as well as treatment, continuing the quest for new knowledge and interventions, and ensuring sustainability of the global response. By and large, progress has been made on all fronts.

After the CAPRISA 004 trial of precoital and postcoital use of tenofovir gel was published in 2010 ( 14 ), the Ring ( 15 ) and Aspire ( 16 ) studies (randomized, placebo-controlled trials in South Africa) examined the protective efficacy of a self-inserted vaginal ring impregnated with slow-release dapivirine, a nonnucleoside reverse transcription inhibitor. The overall efficacy rates for reducing HIV incidence were 31% (Ring) and 27% (Aspire); many questions about overall efficacy, adherence, and differences by age remained. This collective experience provided proof of concept for woman-controlled prevention but did not provide the definitive public health solution to high HIV incidence among young women in Africa.

Four pivotal randomized trials ( 17 – 20 ) of oral preexposure prophylaxis (PrEP) with Truvada (combination of tenofovir and emtricitabine) were pivotal for international licensing of the compound. The relevant trials studied MSM, transgender women having sex with men, and at-risk heterosexual persons. A review of evidence considered another 9 studies, some of tenofovir alone, in different populations including people who inject drugs ( 21 ). The pivotal trials showed reduced HIV incidence (44%–86%) with Truvada use. However, a consistent observation has been a strong association between efficacy and adherence; PrEP is effective, but the drugs need to be taken.

Subsequent research focused on differential tissue penetration of drugs to relevant anatomic sites in men and women and on modes of drug delivery. HIV Prevention Trials Network (HPTN) studies compared the prevention efficacy of the long-acting injectable drug cabotegravir with Truvada in men and transgender women who have sex with men (study 083 [ 22 ]) and in heterosexual women (study 084 [ 23 ]). Interim results showed that cabotegravir, delivered every 8 weeks by injection, was associated with 66% lower incidence than oral Truvada in study 083 and 89% less in study 084. The long half-life of cabotegravir enables intermittent dosing, but waning drug levels over time may become subtherapeutic, thus requiring additional interventions to prevent infection and preclude development of drug resistance.

In its 2016 guidelines, the World Health Organization (WHO) recommended public health use of PrEP, as have other national and international regulatory or advisory bodies. However, the enthusiasm engendered by PreP science needs to be tempered by consideration of cost, need for rigorous adherence, rising rates of other sexually transmitted infections and thus need for continued condom use, and contraception for women. Long-acting injectables could be a major advance, but accessibility and logistics for their delivery need to be considered.

Mathematical modeling and ecologic studies suggested that greatly increased delivery of ART could reduce HIV transmission at the community level. The definitive study showing that ART provided prevention benefits was the landmark HPTN 052 study ( 24 ), published in interim form in 2011. This trial among discordant couples found a 96% reduction in HIV transmission among those who started ART early versus those for whom it was deferred. Combined with an influential modeling study ( 25 ) that suggested that regular HIV testing and immediate use of ART could suppress and perhaps ultimately eliminate HIV transmission, the results of HPTN 052 led to studies in East and southern Africa of the so-called test and treat intervention ( 26 – 29 ). These studies were community randomized evaluations of widespread HIV testing and immediate ART compared with standard care; the primary endpoint was HIV incidence. These large, expensive implementation science studies yielded rich information but did not lead to local HIV elimination. Of the 4 studies, 2 showed no significant incidence reduction and the other 2 showed 20%–30% reduction.

One of the reasons for the unexpectedly modest differences in HIV incidence between intervention and control communities in the test and treat study was changing global practice with regard to when to start ART. In 2015, results of the START ( 30 ) and TEMPRANO ( 31 ) trials showed unequivocally that immediate ART, irrespective of CD4+ lymphocyte count, resulted in reduced HIV-associated disease and death, ending more than 2 decades of argument about when to start treatment. WHO rapidly changed global recommendations to immediately start ART, one result of which was erosion of differences between intervention and control communities in the test and treat trials.

Although test and treat did not reduce HIV incidence to the extent hoped for, the accumulated evidence supports the notion of early, universal ART for extending the lives of HIV-positive persons as well as reducing the prevalence of unsuppressed viremia, the driver of HIV transmission. Large observational studies ( 32 ) showed that persons with suppressed viremia do not transmit the virus sexually, leading to the slogan “U = U”—undetectable equals untransmittable. This experience provides a much more compelling argument for active HIV case finding through increased HIV testing and partner notification, to enhance individual and public health through early treatment.

Although none of the approaches described provides a unique solution, the combination of widespread HIV testing, early ART for those infected, and PrEP for those at risk offers opportunity for substantially limiting the epidemic. Such approaches have been associated with reductions in new HIV infections among MSM in London, UK ( 33 ), and in New South Wales, Australia ( 34 ). In the United States, these advances—testing, case finding including through partner notification, universal treatment, PrEP, and rapid molecular investigation of clusters for service provision—have been incorporated into a revised national strategy for HIV elimination ( 35 ).

Progress toward an HIV vaccine remains discouraging. The only report of protective efficacy, published in 2009, has been the RV-144 study in Thailand ( 36 ), which investigated use of a recombinant canarypox vector vaccine (ALVAC-HIV) delivered in 4 monthly priming injections followed by a recombinant glycoprotein 120 subunit vaccine (AIDSVAX B/E) given in 2 additional injections. Reported efficacy was 26%–31%, but statistical and technical interpretation of these results was controversial ( 37 ). In 2016, the HVTN 702 study was launched in South Africa and used the same product as in the Thailand trial but modified for the dominant subtype C. After interim analysis, the study was halted for futility in early 2020 ( 38 ). Other efficacy studies of vaccines based on so-called mosaic immunogens from diverse HIV subtypes are in progress.

There has been great interest in broadly neutralizing antibodies to HIV, which some infected persons produce naturally and which might protect against a wide variety of strains. Two international trials of infusions with a broadly neutralizing antibody, VRC01, every 8 weeks showed relative protection against sensitive strains but no significantly reduced HIV incidence overall ( 39 ).

In 2014, UNAIDS launched its 90:90:90 initiative, aiming for 90% of persons with HIV infection to be diagnosed, 90% of those with an HIV diagnosis to receive ART, and 90% of those receiving treatment to show viral suppression by 2020. Globally, the respective proportions in 2019 were 81%, 82%, and 88%, so that an estimated 59% of persons living with HIV were showing viral suppression. Initially, 90:90:90 (with a goal of these numbers being 95s by 2030) was an advocacy proposal rather than an evidence-based initiative, but these targets have become adopted as policy promising “epidemic control,” itself a concept requiring precise definition ( 40 ).

ART scale-up, increased male circumcision, and prevention of mother-to-child transmission have all contributed to encouraging advances in the most heavily affected regions of Africa ( 11 , 41 , 42 ). Successful program implementation and declines in new HIV infections and deaths, combined with scientific progress, have led to a certain complacency that “AIDS is over.” Former US Secretary of State Hillary Clinton and staff promoted the idea that current tools could abruptly halt the epidemic. We largely agree with the 2018 judgment of the International AIDS Society–Lancet Commission on AIDS: “The HIV/AIDS community made a serious error by pursuing ‘the end of AIDS’ message” ( 43 ). Key populations, hiding in obscurity as well as in plain sight, will probably remain as reservoirs, even with highly performing programs. Experience in East and southern Africa has highlighted the challenge of adequate service provision to youth and men. Stigma and discrimination remain barriers in many parts of the world, and lack of an HIV cure (a priority research area) and vaccine remain scientific obstacles ( 44 ).

Evolving Global Health

The HIV/AIDS pandemic has evolved in parallel with other global health events that necessarily influence how HIV/AIDS is perceived and prioritized. In a 2012 paper, author K.D.C. suggested that global health trends could best be analyzed through the lenses of development, public health, and health security ( 45 ). The fourth decade of AIDS started in the aftermath of the global financial crisis and the influenza (H1N1) pandemic and is finishing amid the coronavirus disease (COVID-19) pandemic. Although substantial progress has been made toward reducing maternal deaths, improving child survival rates, and scaling up programs for HIV/AIDS, malaria, and tuberculosis, the past decade has seen major disease outbreaks and a consequent focus on health security. Because of its sociodemographic effects, AIDS was portrayed as a security issue in United Nations discussions early in this century. With massive scale-up of treatment and prevention, HIV/AIDS is now perceived as another public health priority rather than a security emergency.

In 2014, Ebola was reported in Guinea, Liberia, and Sierra Leone, far west of previously recognized outbreaks. The epidemic lasted until mid-2016 and ultimately resulted in 28,646 reported cases and 11,323 deaths ( 46 ). Infections were exported to 3 other countries in Africa, several countries in Europe, and the United States. This health crisis resulted in widespread fear of possible global spread, unparalleled global mobilization of emergency health assistance including use of armed forces of the different high-income countries, and political involvement at the highest levels of governments and the United Nations. Subsequent outbreaks of Ebola have occurred in Uganda and the Democratic Republic of the Congo (DRC), including a large epidemic in conflict-ridden eastern DRC in 2018–2020 that resulted in 3,481 reported cases and 2,299 deaths ( 47 ). Underemphasized aspects of these Ebola epidemics were that cases over the past 6 years represent more than 90% of all cases reported cumulatively since recognition of Ebola in 1976; that vast geographic distances were involved; and that these outbreaks were largely urban, sometimes involving capital and other major cities. Ebola epidemiology has changed from that of an exotic, remote infection in Africa to one capable of causing extensive urban outbreaks threatening global health ( 48 ). Also of note was that field research conducted during the outbreaks under the most difficult conditions showed efficacy of a vaccine and therapeutics, both now considered the standard of care for Ebola ( 49 , 50 ).

Over the past decade, arboviral epidemic activity has been diverse. The epidemics of yellow fever in Angola and the DRC in 2015–2016 were the world’s largest over the past 30 years. A total of 965 cases and 400 deaths were reported, but true numbers were far greater. Over 30 million persons were vaccinated, and shortage of yellow fever vaccine required healthcare providers to resort to the untested practice of fractionating vaccine doses ( 51 ). Huge epidemics of chikungunya and dengue occurred internationally; virus was transmitted to areas previously considered at low risk, such as Europe ( 52 ). In 2015, the Zika epidemic raised global concern when infection with this virus was shown to be associated with microcephaly in infants and with Guillain-Barré syndrome and to be sexually transmissible. The outbreak resulted in at least 3,700 cases of birth defects in the Americas ( 53 ).

In 2005, after the outbreak of severe acute respiratory syndrome (SARS), WHO revised its International Health Regulations ( 54 ). A key change was authority to declare a Public Health Emergency of International Concern, a health emergency that could result in international spread or required coordinated action. WHO has implemented this authority only 6 times, 5 of them during the fourth decade of AIDS: for polio (2014), Ebola (2014 and 2019), Zika (2015), and COVID-19 (2019).

Related to health security are the interrelated challenges of global warming, demographic change, and migration. Climate change affects social and environmental determinants of health, such as access to clean air, water, shelter, and arable lands, but also exerts direct health effects. The United Nations High Commissioner for Refugees characterized 2010–2019 as “a decade of displacement,” during which 100 million persons were forced to flee their homes, many because of conflict such as that in the Middle East. During 2014–2020, some 20,000 migrants crossing the Mediterranean Sea to Europe drowned, and another 12,000 or more were unaccounted for.

Broad themes that have dominated global health discourse include the transition from the era of the Millennium Development Goals (MDGs; 2000–2015) to that of the broader Sustainable Development Goals (SDGs; 2015–2030) ( 55 ) and the issue of universal health coverage. Other disease-specific programs require continued support, such as the unfinished efforts to eradicate polio and Guinea worm disease. The MDGs had 3 specific health goals relating to child survival; maternal health; and HIV/AIDS, tuberculosis, and malaria. Only 1 of the 17 SDGs is devoted to health, SDG3, which has 13 targets and 28 indicators. Specifically, SDG3 calls for: “By 2030, end the epidemics of AIDS, tuberculosis, malaria and neglected tropical diseases and combat hepatitis, water-borne diseases and other communicable diseases.” Another target and WHO priority is provision of universal health coverage, global access to decent healthcare, and protection against penury from out-of-pocket health expenditures. HIV/AIDS exists in a crowded and complex global health space.

Preparing for the Fifth Decade of AIDS

As the world emerged from the financial crisis a decade ago, there was concern that HIV/AIDS funding might be constrained. Development assistance for health reached $40.6 billion in 2019, an increase of 15% over the amount in 2010 ( 56 ). Approximately half of this assistance goes to HIV/AIDS, especially for treatment, and to newborn, maternal, and child health. Thus, although health security has eclipsed health development and global public health in this fourth decade of AIDS, financial commitments have been largely maintained.

The overall annual spending on HIV/AIDS by low- and middle-income countries is ≈$20.2 billion, of which ≈$9.5 billion represents donor funding. UNAIDS consistently communicates that to meet SDG targets, overall spending on HIV/AIDS needs to increase by ≈40%. Nonetheless, this HIV-specific spending is privileged compared with funding for other high-impact diseases in low-income settings, such as malaria and tuberculosis. AIDS is no longer among the 10 leading causes of death globally and is now widely viewed as a medically manageable disease. HIV/AIDS prioritization and funding may be justified by the youthful groups affected and its lifelong nature, but this view may be increasingly challenged. Expecting the United States to pay indefinitely for most of the world’s HIV/AIDS response is unrealistic. The end of the SDG era in 2030 will probably come with reappraisal of global commitments, including those for global health funding, disease-specific focus, and maintenance of single-disease organizations such as UNAIDS. Over the coming years, HIV/AIDS programs need to show good fiscal management and epidemiologic results, and affected countries need to shoulder an increased share of their disease burdens.

Lessons from HIV/AIDS and Other Epidemics

The most dramatic epidemics in recent time (COVID-19 [ 57 ], Ebola, and HIV/AIDS) involve quite different biological agents and challenges yet also raise common themes and questions. Especially needed are global responses to challenges that transcend national borders. Pathogen emergence is enhanced by globalization, but globalized systems are needed to address an interconnected worldwide emergency. The slogan “no one is safe until everyone is safe” has been heard in relation to COVID-19, but it was said years ago about HIV. And global health needs global funding.

Individual leaders and organizations have performed valiant work on COVID-19, yet countries have isolated themselves in all senses, resulting in global fragmentation. Major powers look inward yet are reluctant to cede space, and the influence of multilateral agencies is limited. WHO was heavily criticized after the Ebola epidemic in West Africa but is constrained by restricted authority, inadequate funding, and unrealistic expectations from member states. Repeated calls for WHO reform are unclear about what is really wanted.

Honesty is required concerning preparedness and surveillance. The Ebola epidemic in West Africa became as severe as it did because the 3 affected countries had been neglected for years and had no functioning surveillance and public health infrastructure. We cannot say that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was completely unexpected; the literature on pandemic threats is voluminous. SARS in 2002–2003 was severe but not widespread; the 2009 influenza (H1N1) pandemic was widespread but not severe. It is hubristic to assume that pathogen severity and spread would always segregate, yet we were not prepared. Preparedness metrics can give false reassurance, witnessed by the lamentable response to COVID-19 in the United States in 2020. “Never again” was the mood after the Ebola epidemic in West Africa, but preparedness just seems too hard and costly. Perhaps true preparedness exists only in the military, where personnel train continuously for wars they hope will never happen.

As a result of technologic advances such as whole-genome sequencing, scientific progress on COVID-19 has been breathtakingly rapid compared with early laboratory research on HIV. We hope to not see a replay of the early history of ART, with scientific advances relating to COVID-19, and specifically vaccines, not being rapidly or equitably accessible everywhere. “Vaccine nationalism” is a new term raising the specter of lower risk groups in high-income countries receiving vaccine before, for example, frontline healthcare workers in low-income settings. Healthcare workers have been disproportionately affected by Ebola and COVID-19, highlighting the need for much greater investment in infection prevention and control in healthcare settings worldwide. Attention and innovation are required to ensure maintenance of HIV and other essential public health services amid other outbreaks such as COVID-19.

Although initially slow, the HIV/AIDS response over the years has been a beacon in global health for respect for individuals and their rights and for health equity. More reflection is required with regard to what the responses to HIV and Ebola have taught us and how they might be relevant to COVID-19 and other future epidemics.

Conclusions

Although great need remains, the past decade has seen scientific and programmatic successes with regard to the HIV/AIDS priorities we defined after 30 years of AIDS. Existing interventions have been scaled up, and new tools such as PrEP and long-lasting drug preparations have been introduced. The roles of HIV testing and ART for treatment and prevention have been clarified, and the need for immediate ART for all HIV-infected persons has been proven. The global HIV/AIDS response has been sustained, financing has been maintained, and the world has kept focus on the SDGs. Mann’s judgment that “we did not separate ourselves” remains justified. We must also accept that political promises of “the end of AIDS” were hyperbole that current epidemiology does not support.

The COVID-19 pandemic has exploited the fault lines of global systems and existing inequalities in a way that HIV did early on. Regrettably, the solidarity that HIV/AIDS engendered has not yet been carried over. In retrospect, the recent epidemics of Ebola in West Africa and DRC were preparation for the COVID-19 pandemic, but follow-through was lacking. The fifth decade of AIDS will take us to the SDG target date and reassessment of global health and development priorities. HIV/AIDS may not be central to global health discourse as it was earlier, but it will remain a yardstick by which to judge commitment and efforts, including, and especially in relation to, health security.

On February 7, 2021, the Ministry of Health of DRC reported a laboratory-confirmed case of Ebola in North Kivu Province, the most heavily affected province during the 2018–2020 outbreak in eastern Congo. The case-patient experienced symptom onset on January 25, 2021, and died in Butembo, a city of ≈1 million persons, on February 4, 2021. She was reportedly linked epidemiologically to an Ebola survivor, and genetic sequencing reportedly showed phylogenetic association with the earlier outbreak rather than a new spillover event. As of February 8, 2021, a total of 118 contacts were being investigated ( https://www.who.int/emergencies/diseases/ebola/ebola-2021-north-kivu , https://www.who.int/csr/don/10-february-2021-ebola-drc/en ).

Separately, on February 14, 2021, the Ministry of Health of the Republic of Guinea reported an outbreak of Ebola in the subprefecture of Gouécké, Nzérékoré Region, the first report of Ebola in Guinea since the 2014–2016 epidemic. The index case-patient, a nurse, experienced symptoms on January 18, 2021, and died on January 28, 2021. A total of 6 secondary Ebola cases were reported, 1 in a traditional practitioner who cared for the index case-patient and 5 in family members attending her subsequent funeral. Of the 7 case-patients, 5 died. As of February 15, 2021, a total of 192 contacts were being investigated, including in the capital city, Conakry ( https://www.who.int/emergencies/diseases/ebola/ebola-2021-nzerekore-guinea , https://www.who.int/csr/don/17-february-2021-ebola-gin/en ).

Dr. De Cock retired from CDC in December 2020. He had previously served as founding director of Projet RETRO-CI, Abidjan, Côte d’Ivoire; director of the CDC Division of HIV/AIDS Prevention, Surveillance and Epidemiology; director of the WHO Department of HIV/AIDS; founding director of the CDC Center for Global Health; and director, CDC Kenya.

  • Centers for Disease Control (CDC) . Pneumocystis pneumonia—Los Angeles. MMWR Morb Mortal Wkly Rep . 1981 ; 30 : 250 – 2 . PubMed Google Scholar
  • De Cock  KM , Jaffe  HW , Curran  JW . Reflections on 30 years of AIDS. Emerg Infect Dis . 2011 ; 17 : 1044 – 8 . DOI PubMed Google Scholar
  • Centers for Disease Control and Prevention . Compendium of evidence-based interventions and best practices for HIV prevention [ cited 2021 Apr 18 ]. https://www.cdc.gov/hiv/research/interventionresearch/compendium/index.html
  • Barré-Sinoussi  F , Chermann  J-C , Rey  F , Nugeyre  MT , Chamaret  S , Gruest  J , et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science . 1983 ; 220 : 868 – 71 . DOI PubMed Google Scholar
  • Popovic  M , Sarngadharan  MG , Read  E , Gallo  RC . Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science . 1984 ; 224 : 497 – 500 . DOI PubMed Google Scholar
  • Hahn  BH , Shaw  GM , De Cock  KM , Sharp  PM . AIDS as a zoonosis: scientific and public health implications. Science . 2000 ; 287 : 607 – 14 . DOI PubMed Google Scholar
  • France  D . How to survive a plague: the inside story of how citizens and science tamed AIDS. New York: Alfred Knopf; 2016 .
  • Merson  M , Inrig  S . The AIDS pandemic. Searching for a global response. 2018 . Cham (Switzerland); Springer International Publishing; 2018. p. 25–113.
  • Piot  P . No time to lose. A life in pursuit of deadly viruses. New York: W.W. Norton & Co.; 2012 . p. 316–34.
  • Fauci  AS , Eisinger  RW . PEPFAR—15 years and counting the lives saved. N Engl J Med . 2018 ; 378 : 314 – 6 . DOI PubMed Google Scholar
  • Joint United Nations Programme on HIV/AIDS . UNAIDS data 2020 [ cited 2021 Apr 18 ]. https://www.unaids.org/sites/default/files/media_asset/2020_aids-data-book_en.pdf
  • Centers for Disease Control and Prevention . HIV surveillance report, 2018 (Preliminary); vol. 30 [ cited 2021 Mar 14 ]. https://www.cdc.gov/hiv/library/reports/hiv-surveillance.html
  • Peters  PJ , Pontones  P , Hoover  KW , Patel  MR , Galang  RR , Shields  J , et al. ; Indiana HIV Outbreak Investigation Team . HIV infection linked to injection use of oxymorphone in Indiana, 2014–2015. N Engl J Med . 2016 ; 375 : 229 – 39 . DOI PubMed Google Scholar
  • Abdool Karim  Q , Abdool Karim  SS , Frohlich  JA , Grobler  AC , Baxter  C , Mansoor  LE , et al. ; CAPRISA 004 Trial Group . Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science . 2010 ; 329 : 1168 – 74 . DOI PubMed Google Scholar
  • Nel  A , van Niekerk  N , Kapiga  S , Bekker  L-G , Gama  C , Gill  K , et al. ; Ring Study Team . Safety and efficacy of a dapivirine vaginal ring for HIV prevention in women. N Engl J Med . 2016 ; 375 : 2133 – 43 . DOI PubMed Google Scholar
  • Baeten  JM , Palanee-Phillips  T , Brown  ER , Schwartz  K , Soto-Torres  LE , Govender  V , et al. ; MTN-020–ASPIRE Study Team . Use of a vaginal ring containing dapivirine for HIV-1 prevention in women. N Engl J Med . 2016 ; 375 : 2121 – 32 . DOI PubMed Google Scholar
  • Grant  RM , Lama  JR , Anderson  PL , McMahan  V , Liu  AY , Vargas  L , et al. ; iPrEx Study Team . Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med . 2010 ; 363 : 2587 – 99 . DOI PubMed Google Scholar
  • Baeten  JM , Donnell  D , Ndase  P , Mugo  NR , Campbell  JD , Wangisi  J , et al. ; Partners PrEP Study Team . Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med . 2012 ; 367 : 399 – 410 . DOI PubMed Google Scholar
  • McCormack  S , Dunn  DT , Desai  M , Dolling  DI , Gafos  M , Gilson  R , et al. Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial. Lancet . 2016 ; 387 : 53 – 60 . DOI PubMed Google Scholar
  • Molina  J-M , Capitant  C , Spire  B , Pialoux  G , Cotte  L , Charreau  I , et al. ; ANRS IPERGAY Study Group . On-demand preexposure prophylaxis in men at high risk for HIV-1 infection. N Engl J Med . 2015 ; 373 : 2237 – 46 . DOI PubMed Google Scholar
  • National Institute for Health and Care Excellence . Pre-exposure prophylaxis of HIV in adults at high risk: Truvada (emtricitabine/tenofovir disoproxil). Evidence summary. [ESNM78] [ cited 2021 Mar 14 ]. https://www.nice.org.uk/advice/esnm78/chapter/full-evidence-summary
  • National Institutes of Health . Long-acting injectable form of HIV prevention outperforms daily pill in NIH study [ cited 2021 Apr 18 ]. https://www.nih.gov/news-events/news-releases/long-acting-injectable-form-hiv-prevention-outperforms-daily-pill-nih-study
  • National Institutes of Health . NIH study finds long-acting injectable drug prevents HIV acquisition in cisgender women [ cited 2021 Apr 18 ]. https://www.nih.gov/news-events/news-releases/nih-study-finds-long-acting-injectable-drug-prevents-hiv-acquisition-cisgender-women
  • Cohen  MS , Chen  YQ , McCauley  M , Gamble  T , Hosseinipour  MC , Kumarasamy  N , et al. ; HPTN 052 Study Team . Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med . 2011 ; 365 : 493 – 505 . DOI PubMed Google Scholar
  • Granich  RM , Gilks  CF , Dye  C , De Cock  KM , Williams  BG . Universal voluntary HIV testing with immediate antiretroviral therapy as a strategy for elimination of HIV transmission: a mathematical model. Lancet . 2009 ; 373 : 48 – 57 . DOI PubMed Google Scholar
  • Iwuji  CC , Orne-Gliemann  J , Larmarange  J , Balestre  E , Thiebaut  R , Tanser  F , et al. ; ANRS 12249 TasP Study Group . Universal test and treat and the HIV epidemic in rural South Africa: a phase 4, open-label, community cluster randomised trial. Lancet HIV . 2018 ; 5 : e116 – 25 . DOI PubMed Google Scholar
  • Havlir  DV , Balzer  LB , Charlebois  ED , Clark  TD , Kwarisiima  D , Ayieko  J , et al. HIV testing and treatment with the use of a community health approach in rural Africa. N Engl J Med . 2019 ; 381 : 219 – 29 . DOI PubMed Google Scholar
  • Makhema  J , Wirth  KE , Pretorius Holme  M , Gaolathe  T , Mmalane  M , Kadima  E , et al. Universal testing, expanded treatment, and incidence of HIV infection in Botswana. N Engl J Med . 2019 ; 381 : 230 – 42 . DOI PubMed Google Scholar
  • Hayes  RJ , Donnell  D , Floyd  S , Mandla  N , Bwalya  J , Sabapathy  K , et al. ; HPTN 071 (PopART) Study Team . HPTN 071 (PopART) Study Team. Effect of universal testing and treatment on HIV incidence—HPTN 071 (PopART). N Engl J Med . 2019 ; 381 : 207 – 18 . DOI PubMed Google Scholar
  • Lundgren  JD , Babiker  AG , Gordin  F , Emery  S , Grund  B , Sharma  S , et al. ; INSIGHT START Study Group . Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med . 2015 ; 373 : 795 – 807 . DOI PubMed Google Scholar
  • Danel  C , Moh  R , Gabillard  D , Badje  A , Le Carrou  J , Ouassa  T , et al. ; TEMPRANO ANRS 12136 Study Group . TEMPRANO ANRS 12136 Study Group. A trial of early antiretrovirals and isoniazid preventive therapy in Africa. N Engl J Med . 2015 ; 373 : 808 – 22 . DOI PubMed Google Scholar
  • Rodger  AJ , Cambiano  V , Bruun  T , Vernazza  P , Collins  S , van Lunzen  J , et al. ; PARTNER Study Group . Sexual activity without condoms and risk of HIV transmission in serodifferent couples when the HIV-positive partner is using suppressive antiretroviral therapy. JAMA . 2016 ; 316 : 171 – 81 . DOI PubMed Google Scholar
  • Nwokolo  N , Hill  A , McOwan  A , Pozniak  A . Rapidly declining HIV infection in MSM in central London. Lancet HIV . 2017 ; 4 : e482 – 3 . DOI PubMed Google Scholar
  • Grulich  AE , Guy  R , Amin  J , Jin  F , Selvey  C , Holden  J , et al. ; Expanded PrEP Implementation in Communities New South Wales (EPIC-NSW) research group . Population-level effectiveness of rapid, targeted, high-coverage roll-out of HIV pre-exposure prophylaxis in men who have sex with men: the EPIC-NSW prospective cohort study. Lancet HIV . 2018 ; 5 : e629 – 37 . DOI PubMed Google Scholar
  • Fauci  AS , Redfield  RR , Sigounas  G , Weahkee  MD , Giroir  BP . Ending the HIV epidemic: a plan for the United States. JAMA . 2019 ; 321 : 844 – 5 . DOI PubMed Google Scholar
  • Rerks-Ngarm  S , Pitisuttithum  P , Nitayaphan  S , Kaewkungwal  J , Chiu  J , Paris  R , et al. ; MOPH-TAVEG Investigators . Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med . 2009 ; 361 : 2209 – 20 . DOI PubMed Google Scholar
  • Desrosiers  RC . Protection against HIV acquisition in the RV144 trial. J Virol . 2017 ; 91 : e00905 – 17 . DOI PubMed Google Scholar
  • National Institutes of Health . Experimental HIV vaccine regimen ineffective in preventing HIV [ cited 2021 Apr 18 ]. https://www.niaid.nih.gov/news-events/experimental-hiv-vaccine-regimen-ineffective-preventing-hiv
  • National Institutes of Health . Antibody infusions prevent acquisition of some HIV strains, NIH studies find [ cited 2021 Apr 18 ]. https://www.niaid.nih.gov/news-events/antibody-infusions-prevent-acquisition-some-hiv-strains-nih-studies-find
  • Ghys  PD , Williams  BG , Over  M , Hallett  TB , Godfrey-Faussett  P . Epidemiological metrics and benchmarks for a transition in the HIV epidemic. PLoS Med . 2018 ; 15 : e1002678 . DOI PubMed Google Scholar
  • Grabowski  MK , Serwadda  DM , Gray  RH , Nakigozi  G , Kigozi  G , Kagaayi  J , et al. ; Rakai Health Sciences Program . HIV prevention efforts and incidence of HIV in Uganda. N Engl J Med . 2017 ; 377 : 2154 – 66 . DOI PubMed Google Scholar
  • Borgdorff  MW , Kwaro  D , Obor  D , Otieno  G , Kamire  V , Odongo  F , et al. HIV incidence in western Kenya during scale-up of antiretroviral therapy and voluntary medical male circumcision: a population-based cohort analysis. Lancet HIV . 2018 ; 5 : e241 – 9 . DOI PubMed Google Scholar
  • Das  P , Horton  R . Beyond the silos: integrating HIV and global health. Lancet . 2018 ; 392 : 260 – 1 . DOI PubMed Google Scholar
  • Eisinger  RW , Fauci  AS . Ending the HIV/AIDS Pandemic. Emerg Infect Dis . 2018 ; 24 : 413 – 6 . DOI PubMed Google Scholar
  • De Cock  KM , Simone  PM , Davison  V , Slutsker  L . The new global health. Emerg Infect Dis . 2013 ; 19 : 1192 – 7 . DOI PubMed Google Scholar
  • Lo  TQ , Marston  BJ , Dahl  BA , De Cock  KM . Ebola: Anatomy of an Epidemic. Annu Rev Med . 2017 ; 68 : 359 – 70 . DOI PubMed Google Scholar
  • World Health Organization . Ending an Ebola outbreak in a conflict zone [ cited 2021 Apr 18 ]. https://storymaps.arcgis.com/stories/813561c780d44af38c57730418cd96cd
  • Arwady  MA , Bawo  L , Hunter  JC , Massaquoi  M , Matanock  A , Dahn  B , et al. Evolution of ebola virus disease from exotic infection to global health priority, Liberia, mid-2014. Emerg Infect Dis . 2015 ; 21 : 578 – 84 . DOI PubMed Google Scholar
  • Mulangu  S , Dodd  LE , Davey  RT Jr , Tshiani Mbaya  O , Proschan  M , Mukadi  D , et al. ; PALM Writing Group ; PALM Consortium Study Team . PALM Consortium Study Team. A randomized, controlled trial of Ebola virus disease therapeutics. N Engl J Med . 2019 ; 381 : 2293 – 303 . DOI PubMed Google Scholar
  • Henao-Restrepo  AM , Camacho  A , Longini  IM , Watson  CH , Edmunds  WJ , Egger  M , et al. Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!). Lancet . 2017 ; 389 : 505 – 18 . DOI PubMed Google Scholar
  • World Health Organization . Yellow fever outbreak Angola, Democratic Republic of the Congo and Uganda 2016–2017 [ cited 2021 Mar 14 ]. https://www.who.int/emergencies/yellow-fever/en
  • Paixão  ES , Teixeira  MG , Rodrigues  LC . Zika, chikungunya and dengue: the causes and threats of new and re-emerging arboviral diseases. BMJ Glob Health . 2018 ; 3 ( Suppl 1 ): e000530 . DOI PubMed Google Scholar
  • Musso  D , Ko  AI , Baud  D . Zika virus infection—after the pandemic. N Engl J Med . 2019 ; 381 : 1444 – 57 . DOI PubMed Google Scholar
  • World Health Organization . International Health Regulations (2005). 2nd ed. Geneva: The Organization; 2008 .
  • United Nations . The 17 goals [ cited 2021 Apr 18 ]. https://sdgs.un.org/goals
  • Institute for Health Metrics and Evaluation . Financing global health 2019 . Tracking health spending in a time of crisis [ cited 2021 Mar 14 ]. http://www.healthdata.org/policy-report/financing-global-health-2019-tracking-health-spending-time-crisis
  • World Health Organization . Weekly epidemiological update on COVID-19—13 April 2021 [ cited 2021 Apr 27 ].  https://www.who.int/publications/m/item/weekly-epidemiological-update-on-covid-19---13-april-2021

DOI: 10.3201/eid2706.210284

Original Publication Date: April 29, 2021

Table of Contents – Volume 27, Number 6—June 2021

Please use the form below to submit correspondence to the authors or contact them at the following address:

Kevin M. De Cock, c/o Miriam McNally, 669 Palmetto Ave, Suites H–I, Chico, CA 95926, USA, and PO Box 25705-00603, Lavington, Nairobi, Kenya

Comment submitted successfully, thank you for your feedback.

There was an unexpected error. Message not sent.

Exit Notification / Disclaimer Policy

  • The Centers for Disease Control and Prevention (CDC) cannot attest to the accuracy of a non-federal website.
  • Linking to a non-federal website does not constitute an endorsement by CDC or any of its employees of the sponsors or the information and products presented on the website.
  • You will be subject to the destination website's privacy policy when you follow the link.
  • CDC is not responsible for Section 508 compliance (accessibility) on other federal or private website.

Article Citations

Highlight and copy the desired format.

Metric Details

Article views: 8678.

Data is collected weekly and does not include downloads and attachments. View data is from .

Citations: 47

What is the altmetric attention score.

The Altmetric Attention Score for a research output provides an indicator of the amount of attention that it has received. The score is derived from an automated algorithm, and represents a weighted count of the amount of attention Altmetric picked up for a research output.

researchers in a lab

CDC provides national leadership for HIV prevention research, including the development and evaluation of HIV biomedical and behavioral interventions to prevent HIV transmission and reduce HIV disease progression in the United States and internationally. CDC’s research efforts also include identifying those scientifically proven, cost-effective, and scalable interventions and prevention strategies to be implemented as part of a high-impact prevention approach for maximal impact on the HIV epidemic.

The AIDS epidemic, although first recognized only 20 years ago, has had a profound impact in communities throughout the United States.

The Serostatus Approach to Fighting the HIV Epidemic: Prevention Strategies for Infected Individuals R. S. Janssen, D. R. Holtgrave, and K. M. De Cock led the writing of this commentary. R. O. Valdiserri, M. Shepherd, and H. D. Gayle contributed ideas and helped with writing and reviewing the manuscript.

Reports

CDC has provided funding to HIV partners to help implement programs that will help curb the increase of HIV infections. These programs facilitated with our partners and grantees are critical in the goal of eliminating HIV infection in the United States.

Research

CDC has researched several HIV prevention interventions that have proven effective in helping to prevent HIV infection in certain populations and communities.

Demonstration Projects

CDC has worked with key cities to create effective policies and programs to curb the tide of HIV infections in those cities. These cities have higher rates of HIV due to a number of factors therefore making them key locations for studies.

MMP

The Medical Monitoring Project (MMP) is a surveillance system designed to learn more about the experiences and needs of people who are living with HIV. It is supported by several government agencies and conducted by state and local health departments along with the Centers for Disease Control and Prevention.

  • Assessment of 2010 CDC-funded Health Department HIV Testing Spending and Outcomes pdf icon [PDF – 359 KB]
  • HIV Testing Trends in the United States, 2000-2011 pdf icon [PDF – 1 MB]
  • HIV Testing at CDC-Funded Sites, United States, Puerto Rico, and the U.S. Virgin Islands, 2010 pdf icon [PDF – 691 KB]
  • HIV Prevention Funding Allocations at CDC-Funded State and Local Health Departments, 2010 pdf icon [PDF – 792 KB]

Cost-effectiveness of HIV Prevention

  • The cost-effectiveness of HIV prevention efforts has long been a criterion in setting program priorities. The basic principle is straightforward: choose those options that provide the greatest outcome for the least cost.
  • The fact sheet Projecting Possible Future Courses of the HIV Epidemic in the United States pdf icon compares the cost-effectiveness of three different prevention investment scenarios.

The HIV/AIDS Prevention Research Synthesis (PRS) Project identifies evidence-based HIV behavioral interventions (EBIs) listed in the Compendium of Evidence-Based HIV Behavioral Interventions to help HIV prevention planners and providers in the United States choose the interventions most appropriate for their communities.

  • On January 1, 2012, CDC began a new 5-year HIV prevention funding cycle with health departments, awarding $339 million annually.
  • The STD/HIV National Network of Prevention Training Centers provides training for health departments and CBOs on the HIV prevention interventions.
  • HIV by Group
  • HIV Risk and Prevention
  • HIV Nexus: Resources for Clinicians
  • HIV Public Health Partners
  • HIV Resource Library
  • HIV Statistics Center
  • About the Division of HIV Prevention
  • VIH en Español
  • @StopHIVTogether
  • Get Email Updates
  • Send Feedback

Exit Notification / Disclaimer Policy

  • The Centers for Disease Control and Prevention (CDC) cannot attest to the accuracy of a non-federal website.
  • Linking to a non-federal website does not constitute an endorsement by CDC or any of its employees of the sponsors or the information and products presented on the website.
  • You will be subject to the destination website's privacy policy when you follow the link.
  • CDC is not responsible for Section 508 compliance (accessibility) on other federal or private website.
  • U.S. Department of Health & Human Services

National Institutes of Health (NIH) - Turning Discovery into Health

  • Virtual Tour
  • Staff Directory
  • En Español

You are here

Research & training, advances in hiv/aids research.

HIV virions budding and releasing from an infected cell.

For an update on what medical science is doing to fight the global HIV/AIDS pandemic, read a Parade article by NIH Director Francis S. Collins and NIAID Director Anthony S. Fauci, AIDS in 2010: How We're Living with HIV .

Over the past several decades, researchers have learned a lot about the human immunodeficiency virus (HIV) and the disease it causes, acquired immunodeficiency syndrome (AIDS). But still more research is needed to help the millions of people whose health continues to be threatened by the global HIV/AIDS pandemic.

At the National Institutes of Health, the HIV/AIDS research effort is led by the National Institute of Allergy and Infectious Diseases (NIAID). A vast network of NIAID-supported scientists, located on the NIH campus in Bethesda, Maryland, and at research centers around the globe, are exploring new ways to prevent and treat HIV infection, as well as to better understand the virus with the goal of finding a cure. For example, in recent months, NIAID and its partners made progress toward finding a vaccine to prevent HIV infection. Check out other promising areas of NIAID-funded research on HIV/AIDS at http://www.niaid.nih.gov/topics/hivaids/Pages/Default.aspx .

Other NIH institutes, including the Eunice Kennedy Shriver National Institute of Child Health and Human Development and National Institute on Alcohol Abuse and Alcoholism, also support research to better control and ultimately end the HIV/AIDS pandemic. Some of these researchers have found a simple, cost-effective way to cut HIV transmission from infected mothers to their breastfed infants. Others have developed an index to help measure the role of alcohol consumption in illness and death of people with HIV/AIDS.

Scanning electron micrograph of HIV particles infecting a human T cell.

Find out more about these discoveries and what they mean for improving the health of people in the United States and all around the globe.

This page last reviewed on August 20, 2015

Connect with Us

  • More Social Media from NIH
  • Open access
  • Published: 30 June 2021

Ethics of HIV cure research: an unfinished agenda

  • Karine Dubé   ORCID: orcid.org/0000-0003-3458-1539 1 ,
  • John Kanazawa 1 ,
  • Jeff Taylor 2 , 3 , 4 ,
  • Lynda Dee 5 , 6 ,
  • Nora Jones 7 ,
  • Christopher Roebuck 7 ,
  • Laurie Sylla 8 ,
  • Michael Louella 8 ,
  • Jan Kosmyna 9 ,
  • David Kelly 9 ,
  • Orbit Clanton 10 ,
  • David Palm 4 , 11 ,
  • Danielle M. Campbell 6 , 12 ,
  • Morénike Giwa Onaiwu 9 , 13 ,
  • Hursch Patel 1 ,
  • Samuel Ndukwe 1 ,
  • Laney Henley 1 ,
  • Mallory O. Johnson 14 ,
  • Parya Saberi 14 ,
  • Brandon Brown 15 ,
  • John A. Sauceda 14 &
  • Jeremy Sugarman 16  

BMC Medical Ethics volume  22 , Article number:  83 ( 2021 ) Cite this article

5786 Accesses

6 Citations

22 Altmetric

Metrics details

The pursuit of a cure for HIV is a high priority for researchers, funding agencies, governments and people living with HIV (PLWH). To date, over 250 biomedical studies worldwide are or have been related to discovering a safe, effective, and scalable HIV cure, most of which are early translational research and experimental medicine. As HIV cure research increases, it is critical to identify and address the ethical challenges posed by this research.

We conducted a scoping review of the growing HIV cure research ethics literature, focusing on articles published in English peer-reviewed journals from 2013 to 2021. We extracted and summarized key developments in the ethics of HIV cure research. Twelve community advocates actively engaged in HIV cure research provided input on this summary and suggested areas warranting further ethical inquiry and foresight via email exchange and video conferencing.

Despite substantial scholarship related to the ethics of HIV cure research, additional attention should focus on emerging issues in six categories of ethical issues: (1) social value (ongoing and emerging biomedical research and scalability considerations); (2) scientific validity (study design issues, such as the use of analytical treatment interruptions and placebos); (3) fair selection of participants (equity and justice considerations); (4) favorable benefit/risk balance (early phase research, benefit-risk balance, risk perception, psychological risks, and pediatric research); (5) informed consent (attention to language, decision-making, informed consent processes and scientific uncertainty); and (6) respect for enrolled participants and community (perspectives of people living with HIV and affected communities and representation).

HIV cure research ethics has an unfinished agenda. Scientific research and bioethics should work in tandem to advance ethical HIV cure research. Because the science of HIV cure research will continue to rapidly advance, ethical considerations of the major themes we identified will need to be revisited and refined over time.

Peer Review reports

There have been remarkable scientific advancements in the prevention and treatment of HIV infection [ 1 ]. Nevertheless, the pursuit of a cure for HIV is now a high priority for researchers, funding agencies, governments and people living with HIV (PLWH) for a variety of reasons: the need for lifelong treatment of HIV infection, cumulative toxicities of antiretroviral therapy (ART), adherence challenges, the costs of ART, barriers to accessing ART, and HIV-related social stigma and discrimination [ 2 , 3 , 4 ]. By HIV “cure,” we mean a regimen or intervention capable of either completely eliminating HIV from the body or inducing a state of durable, ART-free virologic suppression in which small quantities of HIV remain but do not actively increase or cause immunological damage. To date, over 250 biomedical studies worldwide are or have been related to discovering a safe, effective, and scalable HIV cure [ 5 ].

While promising, such research is associated with a range of ethical considerations [ 6 , 7 ]. Akin to other early phase research, there have generally been asymmetric benefit/risk profiles in early-phase HIV cure research, with individual research participants bearing the clinical and psychosocial risks while science and society almost solely reaping the benefits [ 7 , 8 ]. This is particularly the case for research involving risky study procedures, such as analytical treatment interruptions (ATIs) where ART is paused during the research. ATIs are currently necessary to determine whether investigational interventions achieved their intended effects of durable virologic suppression in the absence of ART [ 9 ]. In addition to the potential clinical risks to participants, studies employing ATIs may also increase risks to sexual partners of research participants [ 10 , 11 , 12 , 13 , 14 , 15 ].

Emanuel and colleagues identified seven requirements for ethical clinical research: (1) social value , (2) scientific validity , (3) fair participant selection , (4) favorable benefit/risk ratio , (5) independent review , (6) informed consent , and (7) respect for enrolled participants [ 9 ]. Lo and Grady subsequently specified these ethical requirements for HIV cure research [ 6 ], while also articulating the need for collaborative partnerships with, and having respect for affected and vulnerable communities . Sugarman later expanded these ethical considerations to capture the importance of protecting confidentiality, conflict of interest management (both financial and non-financial), and responsible communication of scientific advancements [ 16 ].

Substantial empirical and conceptual bioethics scholarship has followed. As described below, most empirical inquiry in HIV cure research ethics has centered around decision-making and informed consent among potential participants [ 17 , 18 ], as well as the assessment of acceptable risks and benefits of this research [ 8 , 19 , 20 , 21 , 22 , 23 ]. Other aspects that have been examined include scientific uncertainty [ 24 ], the role of inclusion benefits [ 25 , 26 ], incentives [ 27 ], social value [ 3 , 28 , 29 ], the need to leverage developments in HIV prevention, treatment, and cure research [ 30 , 31 ], and the meaningful engagement and involvement of PLWH [ 32 , 33 , 34 , 35 ].

In this paper, we review recent findings and developments in HIV cure research ethics. Based on a scoping review of the literature augmented by input from community advocates involved in HIV cure research, we highlight areas that warrant further ethical inquiry or guidance.

We conducted a scoping review of the HIV cure research ethics literature from July to October 2020 and May 2021. The purpose of this review was to obtain a broad perspective on this specific topic, focused on pivotal literature in the field, and was not intended to provide a systematic synthesis. This type of review is ideal when there is a need to organize emerging information about a topic by mapping the literature to inform potential future research [ 36 , 37 ].

Our work generally followed the PRISMA extension for Scoping Reviews (PRISMA-ScR) framework [ 36 ]. We concentrated our review on peer-reviewed articles published in the English literature from 2013 to 2021. The year 2013 was selected as a baseline since it corresponds to the publication of the Lo and Grady manuscript on ethical points to consider in HIV cure research [ 6 ], which is when other literature related to the ethics of HIV cure research began to emerge. We used PubMed to initially identify articles on the ethical aspects of HIV cure research. The initial search was conducted in July 2020 using the following specific search terms: ‘ethics’ AND ‘HIV cure research’; ‘ethics’ AND ‘HIV remission research’; ‘ethical considerations’ AND ‘HIV cure research’ OR ‘HIV remission research’; ‘informed consent’ AND ‘HIV cure research’ OR ‘HIV remission research’; and ‘risks’ OR ‘benefits’ AND ‘HIV cure research’ OR ‘HIV remission research’. This resulted in 92 articles. We subsequently used citation tracking, pursuing promising references from the articles identified in the initial PubMed searches, adding 16 articles for further consideration. Consistent with the scoping review methodology [ 36 ], we did not employ strict criteria for adjudicating the literature. Articles were selected because they specifically addressed ethical aspects of HIV cure research. After removing duplicates and excluding articles that did not address ethical aspects of HIV cure research, we screened and reviewed 96 articles. Figure  1 provides a flow diagram summarizing the process.

figure 1

PRISMA-ScR flow diagram: ethics of HIV cure-related research (2013–2021)

In reviewing articles, we extracted and organized ethics findings via manual charting. We used the 2013 Lo and Grady framework [ 6 ] to organize the results. Most of the literature we identified fell under six of the eight ethical points to consider in that framework: (1) social value ; (2) scientific validity ; (3) fair selection of participants ; (4) favorable benefit/risk balance ; (5) informed consent ; and (6) respect for enrolled participants and communities . We did not identify much relevant literature directly related to the other two points of the framework, collaborative partnership and independent review . The initial scoping review was prepared by a team of core reviewers (K.D., J.K., M.O.J, P.S., B.B., J.A.S).

We circulated the draft scoping review to twelve community advocates (J.T., L.D., N.J., C.R., L.S., M.L., J.K., D.K., O.C., D.P., D.M.C., M.G.O.) for discussion and comment. Community advocates were selected on the basis of being actively engaged in HIV cure research and providing input on clinical trial protocols as part of the Martin Delaney Collaboratory and AIDS Clinical Trial Groups (ACTG) community advisory boards. Community advocates were asked to indicate areas that they considered important as well as suggest areas for which they would like additional guidance on. Community advocates were also consulted via virtual video conferencing in November–December 2020, without the use of a standard guide. Community comments and the resulting manuscript were circulated and discussed via email until all community advocates agreed with the points discussed and the areas that needed further ethical insight.

We identified relevant literature under the following themes: (1) social value (ongoing and emerging biomedical research and scalability considerations); (2) scientific validity (study design issues, such as the use of analytical treatment interruptions and placebos); (3) fair selection of participants (equity and justice considerations); (4) favorable benefit/risk balance (early phase research, benefit-risk balance, risk perception, psychological risks, and pediatric research); (5) informed consent (attention to language, decision-making, informed consent processes and scientific uncertainty); and (6) respect for enrolled participants and community (perspectives of people living with HIV and affected communities and representation).

Table 1 includes outstanding research ethics questions related to these themes.

Social value : ongoing and emerging biomedical research and scalability considerations

Ongoing and Emerging Biomedical Research : HIV cure research involves a variety of biomedical approaches, including cell and gene therapies [ 38 ], stem cell transplants [ 39 ], immune-based strategies [ 40 , 41 ], early and intensified HIV therapy [ 42 ], and latency-reversing agents [ 43 , 44 ] among others. These strategies can also be used in combination. Each HIV cure research approach has its own unique ethical considerations and these need to be taken into account to assess their ethical acceptability [ 45 ]. For instance, Sugarman outlined considerations for when ATIs following stem cell transplantation should be ethically permissible [ 46 ]. As HIV cure clinical trials are implemented, Institutional Review Boards (IRBs), and their functional equivalents, need to be prepared to evaluate HIV cure research protocols to ensure they are ethically acceptable [ 47 ]. More deliberation may be needed to create guidelines to inform the ethical evaluation of distinct and emerging HIV cure research approaches.

Moreover, an effective HIV cure may require a combination of approaches which has the potential to substantially increase clinical risks compared to standard ART [ 48 , 49 ]. For example, some biomedical HIV cure research is investigating whether two or more interventions with multimodal activity may help deplete persistent HIV reservoirs and strengthen immunity [ 50 ]. Given the complex nature of latent, integrated HIV proviruses [ 43 ], single interventions may not alone result in effective disruption of latency or durable virologic suppression without ART [ 2 , 50 ]. Some biomedical scientists are even asking whether single interventional HIV cure trials should be completely abandoned [ 50 ]. One proposal is to move directly and efficiently from in vitro studies into combination therapy trials in animals, and then into human testing [ 50 ].

Further attention is needed to anticipate the challenges related to the ethical implementation of combinatorial HIV cure strategies. Examples include combination gene-editing approaches [ 51 ], latency-reversing agents in synergy with immune-modifying agents [ 43 , 48 , 49 , 52 , 53 ], or different permutations of broadly-neutralizing antibodies paired with different HIV cure approaches [ 54 , 55 ]. There are now over 20 active HIV cure clinical studies using combination products with intersecting mechanisms underway in the United States alone [ 5 ]. Combination HIV cure regimens will likely involve additive, synergistic, or antagonistic effects; these combinatorial effects will affect how benefit/risk assessments are performed. Their efficiency and feasibility will rest upon the appropriate ethical and regulatory reviews/approval processes. Ensuring that PLWH, providers, and other stakeholders view these complex regimens as acceptable will be critical (discussed further below).

There is no doubt that the field of HIV cure research is rapidly evolving, and that the related ethics considerations must be relevant to these scientific developments. For example, a novel approach has been HIV cure-related research at the end of life. For example, a research cohort has been assembled in the “Last Gift Study” [ 56 ] that includes PLWH who are terminally-ill with a co-morbid condition (e.g., cancer, advanced heart disease, neurodegenerative disease) and seeks to characterize HIV reservoirs in the brain and deep tissues [ 57 , 58 , 59 ]. Drawing on a similar paradigm in the cancer field [ 60 ], a multi-disciplinary group of researchers outlined ethical considerations for conducting HIV cure research with PLWH at the end of life [ 57 ], including: (1) protecting autonomy through informed consent; (2) avoiding exploitation by fostering altruism; (3) preserving favorable benefit/risk balance; (4) safeguarding against vulnerability through participant-centeredness; and (5) involving next-of-kin/loved ones and community stakeholders [ 57 , 61 , 62 , 63 ]. Further, testing HIV cure research interventions in PLWH at the end of life would introduce important ethical complexities since terminally ill PLWH would undergo potentially risky interventions solely to advance science, and not in the hope of alleviating symptoms or prolonging life [ 57 , 64 ]. More work is needed to guide ethics reviews of such novel protocols.

Scalability Considerations : Bioethicists, researchers, and community members have recognized that scalability of interventions is potentially a key factor by which to judge the social value of HIV cure research strategies [ 3 , 7 , 28 , 29 , 45 , 65 , 66 ]. This aligns with the rationale for advancing translational research related to an HIV cure [ 45 , 67 , 68 ]. That is, successful HIV cure modalities should ultimately be translatable from “bench to patients” and be applicable to diverse clinical care settings and populations around the world [ 45 ]. Consequently, to enhance social value, it is essential to consider the ethical and practical challenges related to translating these interventions into real-world settings [ 45 ].

Globally, only an estimated 60% of PLWH are on ART, and the financial sustainability of HIV treatment programs remain uncertain [ 29 ]. A modeling study conducted in South Africa estimated that an HIV cure would have the greatest impact on HIV incidence if the HIV epidemic is not mitigated by 2030, and that an HIV cure should be prioritized for those not able to access ART and achieve viral suppression [ 69 ]. The Bill and Melinda Gates Foundation is engaging industry, government, academic, and community leaders to define a target product profile for a globally scalable HIV cure [ 66 ]. Increased knowledge related to efficacy, toxicity, design, delivery, durability, follow-up, relapse, participant-perceived benefits and risks, and cost-effectiveness will increase the likelihood that an HIV cure research strategy can become a viable option on a global scale [ 3 , 29 , 66 , 70 ]. It will be desirable to predict and essential to precisely and quickly detect loss of viral suppression and resistance in both resource-rich and resource-limited settings [ 66 ]. Challenges related to clinical and laboratory capacity, financing, training, distance to health care providers, and health systems also need to be overcome [ 45 ]. Biological factors such as prevalence of co-occurring conditions (such as the presence of other infectious or non-communicable diseases, and poor nutrition) and differing HIV subtypes will also need to be considered [ 28 ]. To enhance social value, studies will need to be conducted in communities that would most likely benefit from an HIV cure [ 29 ] and successful interventions should become available to the populations that faced the risks of testing the intervention [ 39 , 71 , 72 ]. HIV cure research developments will also need to be synergistically integrated with ongoing HIV prevention and treatment efforts [ 30 , 31 , 45 , 73 ].

Scientific validity : study design considerations—ATIs and use of placebos

Analytical Treatment Interruptions : ATIs remain one of the most controversial topics in HIV cure research, involving considerations for medical, research, and public health ethics [ 9 , 45 , 74 , 75 , 76 ]. In addition to presenting risks to study participants, such as developing acute retroviral syndrome and/or HIV resistance, ATIs present risks of HIV transmission to the sexual partners of participants [ 15 , 77 , 78 , 79 ]. Following two cases of HIV transmission in the context of an ATI [ 14 , 15 , 78 ], a risk mitigation plan was developed to ensure ATIs could be conducted more safely and ethically. This plan included an ATI study disclosure checklist separate from the consent form and pre-exposure prophylaxis (PrEP) navigation resources for partners [ 13 ]. Given the importance placed by many PLWH on becoming and remaining undetectable for HIV so that they do not transmit HIV to partners [ 80 , 81 , 82 ], understanding the ethical challenges related to mitigating risks during ATIs is of paramount importance [ 83 ]. Determining appropriate risk mitigation strategies will further require effective stakeholder engagement in local contexts [ 84 , 85 , 86 ]. Developing self-administered point of care rapid tests to detect and measure viral rebound with clearly delineated ART restart criteria would also help to mitigate risks to participants and the risk of onward HIV transmission during ATIs.

Use of Placebos : As in other research settings, determining the ethical and scientific appropriateness of placebo-controlled trials in HIV cure research can be complex [ 7 , 9 ]. After extensive deliberation, a multi-disciplinary group of HIV cure experts concluded that placebo arms should be used where necessary and appropriate to confirm scientific validity of trials [ 9 ]. Moreover, they contended it would be unethical not to use placebo groups when scientifically necessary [ 9 ]. In early exploratory ATI studies, scientists have opted to use historical controls to compare time to HIV rebound [ 9 , 87 ]. To minimize risks, another option would be to establish a placebo cohort that could serve as control for multiple trials occurring contemporaneously. Of note, PLWH may be reluctant to enroll in placebo-controlled trials and go off ART for extended periods of time while not knowing whether they received an experimental intervention [ 9 , 75 , 88 ].

Fair selection of participants : equity and justice considerations

Equity and Justice Considerations : Diversity in clinical trials is a matter of justice [ 45 ]. Populations that may benefit the most from an HIV cure are most often unable to participate or are excluded from clinical trials [ 20 , 45 ]. For HIV cure research, efforts should be made to increase representation of cis- and transgender women, as well as other gender diverse individuals, people of color, people who do not speak English as their primary language, and other under-represented and marginalized groups [ 89 ]. For the HIV cure research enterprise to be truly transformative and forward-looking, research teams will need to be committed to social justice, racial and gender equity, and solidarity in research activities. Further, partner risk mitigation strategies during ATIs, such as the use of PrEP, must be acceptable to diverse populations. Such plans must also be appropriate with respect to gender and sex dynamics, accounting for issues related to stigma, the potential need to incorporate trauma-informed approaches [ 90 ] and the potential for intimate partner violence [ 13 , 91 ].

Favorable benefit/risk balance : early-phase research and additional benefit/risk considerations

Early-Phase Research Considerations : HIV cure research harbors similar ethical challenges to early-phase trials in other areas of medicine [ 92 ]. Yet unlike early-phase cancer trials in which study participants may be terminally ill or otherwise have a poor prognosis, most HIV cure study participants include “otherwise healthy volunteers” who are on highly effective ART [ 20 ]. Current early-phase HIV cure trials represent the inverse of the early years of the HIV epidemic when PLWH’s best chance for survival often meant undertaking significant risk through unproven therapies or participation in early phase treatment trials [ 23 ]. Against a backdrop of highly effective and well-tolerated therapies, current safety thresholds for moving novel anti-HIV therapies forward have become extremely high [ 20 , 23 ]. Additionally, many early-phase HIV cure studies are exploratory with little or no likelihood of being curative or providing direct benefit to participants [ 19 ]. Moreover, there are currently no established standards for assessing the ethical permissibility of risks in early-phase HIV cure trials, especially when novel strategies rely solely on pre-clinical evidence (e.g., data from prior cell and animal studies) to initiate human testing [ 93 ].

The ethical appropriateness of early phase HIV cure research typically relies on the judgments and abilities of researchers, IRBs, and regulatory agencies. In evaluating the ethical permissibility of early-phase HIV cure trials, the risks of interventions and ATIs must be considered along with proposed monitoring procedures and risk mitigation strategies (e.g., when ART resumption is warranted following an ATI).

Another challenge for early-phase HIV cure trials relates to the extent to which participants are motivated by altruism [ 94 ]. When participation is motivated by altruism, participants may be willing to accept greater risk, thus lessening concern regarding potential exploitation [ 57 , 95 ].

Further, uncertainty about whether and when an intervention will have a sufficient intended effect to advance further studies, is an area that needs further attention. Specifically, what are the relevant considerations in determining if it is appropriate to advance particular interventions into larger human trials? Currently, there is no consensus regarding what constitutes sufficient benefits for an intervention to be considered “curative.”

Additional Benefit/Risk Considerations : There are a variety of issues related to benefit/risk considerations in the ethics literature on HIV cure research: acceptable benefit/risk balance, risk perceptions, psychosocial benefits and harms, and those particular to pediatric HIV cure research.

Acceptable Benefit/Risk Balance : Major research guidelines require that clinical trials maintain an acceptable benefit/risk balance [ 8 , 96 , 97 ], yet limited concrete and practical guidance exists to help ensure this requirement is met [ 98 , 99 , 100 ]. Maintaining an acceptable benefit/risk balance is necessary because it not only minimizes harming participants, but also helps protect researchers’ professional integrity and maintain public trust in science [ 23 , 98 , 101 , 102 ]. In most early-phase HIV cure research, the ethical analysis involves a knowledge-risk calculus [ 8 , 103 ] that evaluates whether the potential scientific knowledge and additional data justify the risks. HIV cure research walks a fine line between the safety and tolerability of experimental interventions, and the potential efficacy from an intervention [ 20 ]. Steel argues that regulatory limits on risks are prima facie paternalistic [ 104 ]. To the contrary, Różyńska argues that upper risk limits are justified to protect both the research enterprise and participants from unjustified and excessive risks because of inherent power inequities between investigators and participants [ 102 ]. Thus, there is a need for further deliberation about the acceptable level of risks in this research.

A substantial amount of scholarship has focused on the benefits and risks of HIV cure research [ 8 , 96 , 105 , 106 , 107 ]. Eyal summarized various candidate solutions to keep high-risk HIV cure studies ethical, such as reducing risks through robust pre-clinical data, dose limits, and patient engagement, enhancing benefits to individual participants by making participation appealing, recognizing psychosocial benefits of participation, and building towards societal benefits [ 105 ]. As an example, one research team was able to enhance the benefits of an HIV cure study and augment the clinical care of participants by offering colon cancer screening alongside invasive gut biopsy procedures [ 108 ]. Another proposal by Largent [ 106 ] suggested offering payments to augment the benefit/risk profile.

In evaluating benefit/risk favorability, one must consider the types of interventions, the anticipated risks, the background standard of care, and the health status of trial participants [ 22 ]. Nevertheless, some risks will be difficult, if not impossible, to capture in short-term clinical trials [ 38 ]. For example, some trials may carry long-term toxicity risks such as teratogenicity and gene toxicity that could manifest years after a trial has been completed [ 20 , 94 ]. For most interventions, the United States Food and Drug Administration (FDA) has considered PLWH as “otherwise healthy volunteers” to ascertain acceptable risks, thereby decreasing the threshold of risk that could be tolerated in this population [ 22 , 23 ]. DiGiusto and colleagues described five additional categories of participants in HIV cure cell and gene therapy research: (1) PLWH with significant ART side effects and “treatment fatigue;” (2) PLWH not virally suppressed and with incomplete immune recovery; (3) ART non-responders; (4) PLWH with cancer; and (5) PLWH requiring salvage therapy or cancer treatment (e.g., transplants) [ 39 ]. If participants are not “otherwise healthy,” this may increase the level of risks that could be tolerated in these populations [ 20 ]. For example, while a stem cell transplant would be too risky an undertaking for an “otherwise healthy” individual, it may be justifiable as a means of attempting to cure HIV in a person who is already in need of a transplant to treat their cancer. This strategy was used for two people who were cured of HIV: the late Timothy Ray Brown, known as the “Berlin patient”, who died of cancer more than 12 years after his HIV cure; and Adam Castillejo, sometimes referred to as the “London patient” [ 109 , 110 ].

Increasing attention is being paid to the role of safeguards needed to protect study participants in HIV cure trials to minimize risks [ 9 , 20 , 23 , 75 , 111 ]. Maximizing safety while minimizing burdens of monitoring visits (e.g., frequent viral load testing during ATIs) is another fundamental tension in clinical trial design [ 75 ]. Added protections have included robust deliberations around trial design [ 9 ], participant selection and inclusion/exclusion criteria [ 9 , 76 ], informed consent [ 9 , 17 , 76 ], monitoring and safety rules [ 9 ], ART restart criteria in the case of ATIs [ 9 , 76 ], and involvement of community advisory boards (CABs) [ 6 ]. Further, as in most clinical research, emergent situations such as the SARS-CoV-2 pandemic precipitate the need for additional safeguards to protect trial participants from undue harm [ 112 , 113 ]. Safeguards are also essential in trials requiring ATIs. Two independent systematic reviews [ 114 , 115 ] showed that brief ATIs (e.g., a few weeks in duration) did not present substantial risk of adverse events (AEs). However, much less is known about the risks involved in extended ATIs (e.g., a few months), involving sustained periods of viremia [ 9 ]. To properly evaluate extended ATIs, it is imperative to understand not only their clinical risks, but also their psychological and social risks.

Psychosocial Benefits and Harms : HIV cure research has also been associated with psychosocial benefits that have been captured through empirical assessments [ 25 , 107 , 116 , 117 , 118 ] and testimonials [ 119 , 120 , 121 ]. These psychosocial benefits include improved sense of purpose, positive outlook, hope, and emotional support [ 26 ]. Understanding the altruism among many HIV cure trial participants helps contextualize the impact of trial participation on people’s lives [ 94 , 107 ]. Providing an activist’s argument that participant values should guide benefit/risk ratio calculations, Evans claims these altruistic benefits should be recognized because they empower PLWH to assume both self-agency and autonomy as well as risks [ 107 ]. In turn, Rennie and colleagues argued that these collateral psychosocial benefits align with the principle of beneficence and advocate for more detailed guidance on how to account for these benefits in regulatory reviews, consent documents, and trial communications [ 25 , 26 ].

Psychological harms include negative mental states and anxiety, such as the fear of developing drug-resistant HIV or passing HIV on to sexual partners as a result of no ART during ATIs [ 15 , 75 , 77 , 81 , 107 , 119 ]. Social harms encompass the risks of disrupting one’s social network and/or increasing stigmatization because of trial participation [ 100 ]. Further, ATIs may also cause confusion by contradicting long-standing messages from HIV care teams regarding the need for sustained ART adherence [ 75 , 80 , 81 ]. Due to some existing HIV criminalization statutes, PLWH may also face legal ramifications should they engage in behavior perceived as likely to transmit HIV to another party during an ATI [ 75 ]. The potential psychological and mental health dimensions of taking part in intensive HIV cure trials should not be minimized, especially protocol designs requiring participants to be off ART for extended periods of time [ 70 , 112 ]. Given the enduring social stigmatization of HIV, both conventional clinical as well as psychological risks should be integrated into potential study benefit/risk calculations.

Risk Perceptions : A body of empirical research has ascertained stakeholder perceptions of acceptable risk thresholds [ 19 , 20 , 88 , 122 ]. This research has revealed disagreements between stakeholder types (e.g., PLWH, regulators, bioethicists, biomedical researchers, and clinicians) regarding what constitutes “too much risk” in HIV cure research [ 20 ]. As the science evolves, the standard of acceptability may shift and clinical risks may become better defined [ 9 , 21 ]. IRBs may also weigh potential benefits and risks differently [ 20 ]. Therefore, some IRBs may allow trials with extended ATIs resulting in sustained periods of viremia to move forward, while others may prevent these trials from proceeding.

Pediatric HIV Cure Research : Pediatric HIV cure research requires attending to some particular benefit/risk considerations because the immune systems of infants and very young children are still developing and, thus, may be qualitatively different from adults. Pediatric and adolescent HIV spans the period from neonate to up to 24 years of age in some jurisdictions, encompassing distinct age groups and developmental stages [ 9 ]. Arguments for enrolling infants, children, and adolescents in HIV cure trials include the need to prevent delaying the availability of future safe and effective interventions to these groups [ 123 ]. However, such an approach is in tension with standard practices of beginning pediatric research only after an intervention has proven to be safe in adults. Further, young people living with HIV might be less likely to be virally suppressed than adults living with HIV due to more frequent disruptions in ART adherence [ 124 ]. Limited guidance exists on how to preserve the benefit/risk balance in these populations, and a modified ethics framework may be necessary. Shah argued that, with the exception of research involving very early ART initiation, experimental approaches such as combination regimens may be too risky and speculative to warrant studying in pediatric groups [ 123 , 125 ]. Consensus appears to have been achieved among experts that ATIs are not recommended for children younger than two years old or those whose HIV infection is resistant to at least two drug classes [ 9 ]. Nevertheless, additional deliberation is needed to ensure the benefit/risk balance of HIV cure trials in these younger populations, and acceptable monitoring procedures for them.

Informed consent : attention to language, decision-making, informed consent processes and scientific uncertainty

Language : There is a substantial literature on the proper use of language to describe HIV cure research, and those who participate in it [ 126 , 127 , 128 , 129 , 130 , 131 , 132 ]. Although not specific to HIV cure research, PLWH have advocated for the use of “people-first” language, such as “people living with HIV” rather than “HIV-infected individuals,” and for the use of the word “participants” or “volunteers” rather than “subjects” to describe those actively participating in research [ 133 , 134 , 135 ]. While HIV cure research is ultimately directed at “cure”, current research efforts have less ambitious goals and predominately focus on enhancing scientific understanding. Consequently, the word “cure” has also been strongly discouraged from use in informed consent documents and related materials to reduce the possibility of false beliefs that participants will be “cured” from early-phase experiments [ 9 , 17 , 136 ]. Some have recommended the use of the word “experiment” to emphasize the uncertain nature of early-phase research as well as the lack of anticipated direct personal benefit [ 126 ].

Decision-Making : Few empirical studies have been conducted for the purpose of understanding the decision-making processes of those who accept or decline participation in HIV cure-related trials. However, a longitudinal decision-making study nested within a Thai acute HIV-infection research cohort [ 74 , 137 , 138 ] found that participants’ decisions to undergo an ATI for research purposes were based on their understanding of their body’s likely responses to being off medications [ 74 , 137 ]. The findings of therapeutic misconception (confusing the intent of the research with clinical care) and therapeutic misestimation (overestimating the probability of direct benefits and underestimating risks) raise ethical concerns in these studies [ 139 , 140 ]. Of note, therapeutic misconception and misestimation are commonly experienced by participants of early phase trials, and are more ethically problematic than therapeutic optimism (the hope for positive outcomes) [ 139 , 141 ]. Similarly, surveys conducted in the ACTG 5366 trial testing a latency-reversing agent and the ACTG 5345 study interrogating biomarkers of viral rebound found that approximately 20% of participants inaccurately reported believing that the trial did not contain any clinical risk [ 116 , 118 ]. Despite such efforts to measure participants’ understanding during biomedical HIV cure trials [ 74 ], there is a lack of consensus on the best way to assess the extent of therapeutic misconception and misestimation, let alone reduce them. Moreover, concerns regarding therapeutic misconception and misestimation may be heightened in low- and middle-income countries (LMICs), particularly in places where research literacy levels are lower and where unproven, questionable HIV “cures” have flooded informal markets for decades [ 142 , 143 , 144 ].

Additionally, how HIV clinicians perceive and communicate aspects of HIV cure trials to patients is unclear [ 88 , 145 , 146 ]. Due to the chronic nature of HIV infection, many PLWH have long-established, trusting relationships with particular clinicians, and these relationships often function as decision-making units when deciding whether to join a clinical trial [ 147 ].

Informed Consent Processes : Concerns have been raised around the clarity, specificity, and consistency of text used in informed consent forms [ 17 ]. A 2014 review of 13 HIV cure-related informed consent forms by Henderson revealed inconsistencies around the descriptions of study aims, risks, and benefits (or lack thereof) of the research, with conflicting messages about the nature versus the likelihood of direct clinical benefits to study participants. Based on their analysis, the authors recommended surrogate endpoints (e.g., reduction in HIV reservoir size) not be portrayed as possible clinical benefits [ 17 ].

In a separate review, Bromwich and colleagues outlined key informed consent challenges for HIV cure research: (1) how trial information is communicated to potential participants, (2) whether potential participants fully understand key features of the clinical trials in which they are being asked to participate, and (3) the degree to which potential study participants’ motivations to enroll in low-benefit/high-risk research are altruistically motivated [ 18 ]. Overall, it seems clear that empirical research and further deliberation is needed to strengthen and improve the quality of informed consent in general [ 148 , 149 , 150 ].

Scientific Uncertainty : The ethical implications of scientific uncertainty have received limited attention in the HIV cure research field [ 24 , 151 , 152 ]. Although risk and uncertainty imply a lack of knowledge about future outcomes, risk refers to the probability and magnitude about possible harms, whereas uncertainty refers to the lack of predictability due to insufficient scientific evidence [ 153 ]. Early-phase research inherently carries more scientific uncertainty than later-phase research [ 154 ].

HIV cure research is fraught with uncertainty, as evidenced by the cases of the Boston patients (who received hematopoietic stem cell transplants) [ 155 , 156 ] and the Mississippi child (who received early ART administration soon after birth) [ 157 , 158 ]. Despite initial beliefs of cure, the Boston patients and Mississippi child experienced viral rebound following periods of undetectability ranging from several months (Boston patients) to more than two years (Mississippi child) after ART was interrupted.

Scientific uncertainty is particularly relevant during the informed consent process around descriptions of ATIs. ATIs involve periods of unpredictable and stochastic rebounds of virus that no currently known biomarker can accurately predict [ 9 ]. Further, the unknown risks of experimental interventions, as well as how results compare between animal models and human testing, present additional uncertainties [ 45 , 93 , 159 ]. Factors, such as small sample sizes, observational study designs versus randomized controlled trials, and varying immunological, virologic, and clinical monitoring strategies, compound scientific uncertainties in the field [ 115 ]. Thus, it may be useful to assess ways to explicitly discuss and consider scientific uncertainty during the informed consent process (e.g., including a separate section on scientific uncertainty in informed consent documents). Additional information about how uncertainty is communicated to, and understood by, participants and the public is also needed.

Respect for enrolled participants and community : perspectives of PLWH and affected communities and representation

Perspectives of PLWH and Affected Communities : Much HIV cure research centers on the biomedical aspects of cure, while far less attention has been placed on the psychosocial context of those for whom a cure is being sought [ 160 ]. There has been limited research evaluating the motivations, perceptions, needs, concerns, desires, tensions, and experiences of PLWH who participate in these trials [ 70 , 160 ]. A comprehensive understanding of how PLWH view and experience these innovative strategies is ethically essential because it preserves respect for affected communities [ 45 ]. Sparked by the 2014 FDA Patient-Focused Drug Development Initiative [ 161 ], and the ensuing Voice of the Patient report for HIV cure research [ 162 ], greater weight and appreciation has been given to PLWH’s preferences in developing novel HIV therapeutic options [ 163 , 164 , 165 ]. Implementing patient-centered research is particularly important given increased focus on health-related quality of life and psychosocial well-being for PLWH [ 166 ].

Incorporating the participant perspective in research can be facilitated through robust interdisciplinary research by integrating bioethicists and socio-behavioral researchers in trial teams [ 70 , 118 , 167 ]. Empirical ethics and socio-behavioral research can help inform prioritization decisions and determining the acceptability of HIV cure research interventions, which may differ in association with various demographic characteristics [ 23 , 45 ]. For example, focus groups conducted in the United States revealed acceptability concerns for somatic HIV cure cell and gene therapy among PLWH, particularly among ethnic and racial minorities [ 168 ]. A discrete choice experiment conducted in Europe among 150 PLWH and 160 HIV care providers revealed that acceptability would increase if clinical risks of cell and gene therapy could be minimized [ 122 ]. As HIV cure clinical trials get implemented globally, we will need to better understand perspectives of PLWH and affected communities in different contexts.

Community Representation : Ultimately, all stakeholders, including patients, providers, government and overall community acceptance will be critical to the success of any HIV cure regimen [ 28 , 32 , 34 , 35 , 45 , 70 , 169 ]. Although good participatory practice guidelines exist for biomedical HIV prevention research [ 170 ], and have been adopted for tuberculosis [ 171 ] and emerging pathogens [ 172 ], these guidelines may not be seamlessly extrapolated to early-phase HIV cure trials. Additional guidance is needed to inform the ethics of engaging communities around ATIs, HIV transmission risk, and relevant standards of care and prevention. Importantly, as discussed above, the science, language, and messaging around HIV cure research remain extremely complex and technical. Participants and communities must be engaged as mutually respected and integral partners in the research enterprise [ 6 , 133 , 173 ]. Communication should be culturally sensitive, prompt, and easily understandable. Community input should be sought and utilized in defining research priorities and decision-making processes. Efforts should also be taken to build meaningful, long-term relationships with relevant communities regarding the goals of HIV cure research, and not simply around specific short-term trials.

Conclusions

HIV cure research ethics has an unfinished agenda, which will require further inquiry and deliberation. Scientific research and bioethics should work in tandem to advance ethical HIV cure research [ 174 ]. While relying on established ethical guidelines, the field must work towards careful use of language, managing expectations, and high-quality informed consent. HIV cure research must have an acceptable benefit/risk balance and account for scientific uncertainty, particularly before interrupting ART and during ATIs. As the science evolves, it will be essential to better understand the perspectives of PLWH and of affected communities to ensure respect of participants, the continuation of successful research efforts and social value. Ethical considerations will need to be grounded in the reality of ongoing trials and local contexts. Researchers conducting clinical trials should make a genuine commitment to meaningful community and stakeholder engagement. Because the science of HIV cure research will continue to rapidly advance, ethical considerations should be revisited and refined. Sufficient financial and human resources should be dedicated to resolving these critical challenges.

Availability of data and materials

Not applicable.

Abbreviations

AIDS Clinical Trials Group

Adverse event

Antiretroviral treatment

Analytical treatment interruption

AntiViral Research Center

Community advisory board

Center for AIDS Prevention Studies

Collaboratory of AIDS Researchers for Eradication

Community Scientific Subcommittee

Delaney AIDS Research Enterprise

Food and Drug Administration

HIV + Aging Research Project-Palm Springs

Human immunodeficiency virus

Institutional review board

Low- and middle-income country

National Institutes of Health

  • People living with HIV

Pre-exposure prophylaxis

Severe Acute Respiratory Syndrome-Coronavirus 2

U.S. DHHS. FDA-Approved HIV Medicines [Internet]. AIDSinfo. 2020 [cited 2020 Apr 28]. Available from: https://aidsinfo.nih.gov/understanding-hiv-aids/fact-sheets/21/58/fda-approved-hiv-medicines

Deeks SG, Lewin SR, Ross AL, Ananworanich J, Benkirane M, Cannon P, et al. International AIDS Society Global Scientific Strategy: towards an HIV Cure 2016. Nat Med. 2016;22(8):839–50.

Article   Google Scholar  

Freedberg KA, Sax PE. Improving on effective antiretroviral therapy: how good will a cure have to be? J Med Ethics. 2017;43(2):71–3.

Granich R, Gupta S, Hall I, Aberle-Grasse J, Hader S, Mermin J. Status and methodology of publicly available national HIV care continua and 90-90-90 targets: a systematic review. PLOS Med. 2017;14(4):e1002253.

TAG. Research Toward a Cure Trials [Internet]. 2021. Available from: http://www.treatmentactiongroup.org/cure/trials .

Lo B, Grady C. Ethical Considerations in HIV Cure Research: Points to Consider. Curr Opin HIV AIDS. 2013;8(3):243–9.

Eyal N, Holtzman LG, Deeks SG. Ethical issues in HIV remission trials. Curr Opin HIV AIDS. 2018;13(5):422–7.

Dresser R. First-in-human HIV-remission studies: reducing and justifying risk. J Med Ethics. 2017;43(2):78–81.

Julg B, Dee L, Ananworanich J, Barouch D, Bar K, Caskey M, et al. Recommendations for analytical treatment interruptions in HIV research trials. Report of a consensus meeting. Lancet HIV. 2019;6(4):e259–68.

Eyal N, Lipsitch M, Bärnighausen T, Wikler D. Risk to study nonparticipants: a procedural approach. PNAS. 2018;115(32):8051–3.

Eyal N, Deeks SG. Risk to nonparticipants in HIV remission studies with treatment interruption: a symposium. J Infect Dis. 2019;220(Suppl 1):1–4.

Dawson L. Human immunodeficiency virus transmission risk in analytical treatment interruption studies: relational factors and moral responsibility. J Infect Dis. 2019;220(Suppl 1):S12-15.

Peluso MJ, Dee L, Campbell D, Taylor J, Hoh R, Rutishauser RL, et al. A collaborative, multidisciplinary approach to HIV transmission risk mitigation during analytic treatment interruption. J Virus Erad. 2020;6:34–7.

Lelièvre J-D, Hocqueloux L. Unintended HIV-1 transmission to a sex partner in a study of a therapeutic vaccine candidate. J Infect Dis. 2019;16:4–5.

Google Scholar  

Ugarte A, Romero Y, Tricas A, Casado C, Garcia F, Leal L. Unintended HIV-1 infection during analytical treatment interruption. J Infect Dis. 2019;221(10):1740–2.

Sugarman J. HIV Cure Research. Expanding the ethical considerations. Ann Intern Med. 2013;159:9–11.

Henderson GE. The ethics of HIV “cure” research: what can we learn from consent forms? AIDS Res Hum Retroviruses. 2014;31(1):1–14.

Bromwich D, Millum JR. Informed consent to HIV cure research. J Med Ethics. 2017;43(2):108–13.

Dubé K, Taylor J, Sylla L, Evans D, Dee L, Burton A, et al. “Well, it’s the risk of the unknown… right?”: a qualitative study of perceived risks and benefits of HIV cure research in the United States. PLoS ONE. 2017;12(1):1–23.

Dubé K, Dee L, Evans D, Sylla L, Taylor J, Brown B, et al. Perceptions of equipoise, risk—benefit ratios, and “otherwise healthy volunteers” in the context of early-phase HIV cure research in the United States: a qualitative inquiry. J Empir Res Hum Res Ethics. 2017;13(1):1–15.

Eyal N, Holtzman LG. Invited Commentary on Dubé et al. (Perceptions of equipoise, risk/benefit ratios, and “otherwise healthy volunteers” in the context of early-phase HIV cure research in the United States—a qualitative inquiry): are HIV-Infected Candidates for Participat. J Empir Res Hum Res Ethics. 2018;13(1):18–22.

Dubé K, Sylla L, Dee L. Reply to Commentary: “Are HIV-infected candidates for participation in risky cure- related studies otherwise healthy”. J Empir Res Hum Res Ethics. 2017;13(1):1–3.

Dubé K, Dee L. Willingness to risk death endpoint in HIV cure-related research with otherwise healthy volunteers is misleading. J Virus Erad. 2020;6:81–4.

Hare C. Risk and radical uncertainty in HIV research. J Med Ethics. 2017;43(2):87–9.

Gilbertson A, Kelly EP, Rennie S, Henderson GE, Kuruc JD, Tucker JD. Indirect benefits in HIV cure clinical research: a qualitative analysis. AIDS Res Hum Retroviruses. 2019;35(1):100–7.

Rennie S, Day S, Mathews A, Gilbertson A, Luseno W, Tucker J, et al. The role of inclusion benefits in ethics committee assessment of research studies. Ethics Hum Res. 2019;41(3):13–22.

Brown B, Galea JT, Davidson P, Khoshnood K. Transparency of participant incentives in HIV research. Lancet HIV. 2016;3(10):e456–7.

Rossouw T, Tucker JD, van Zyl GU, Sikwesi K, Godfrey C. Barriers to HIV remission research in low- and middle-income countries. J Int AIDS Soc. 2017;20(1):1–9.

Ndungu T, McCune JM, Deeks SG. Why and where an HIV cure is needed and how it might be achieved. Nature. 2019;576(April):397–405.

Muccini C, Crowell TA, Kroon E, Sacdalan C, Ramautarsing R, Seekaew P, et al. Leveraging early HIV diagnosis and treatment in thailand to conduct HIV cure research. AIDS Res Ther. 2019;16(25):1–8.

Tucker JD, Gilbertson A, Lo Y-R, Vitória M. Implications of prioritizing HIV cure: new momentum to overcome old challenges in HIV. BMC Infect Dis. 2016;16(1):109.

Day S, Blumberg M, Vu T, Zhao Y, Rennie S, Tucker JD. Stakeholder engagement to inform HIV clinical trials: a systematic review of the evidence. J Int AIDS Soc. 2018;21(S7):e25174.

Lo Y-R, Chu C, Ananworanich J, Excler J-L, Tucker JD. Stakeholder engagement in HIV cure research: lessons learned from other HIV interventions and the way forward. AIDS Patient Care STDS. 2015;29(7):389–99.

Karris MY, Dubé K, Moore AA. What lessons it might teach us? Community engagement in HIV research. Curr Opin HIV AIDS. 2019;12(2):142–9.

Lau J, Smith M, Allan B, Dubé K, Young A, Power J. Time for revolution? Enhancing meaningful involvement of people living with HIV in HIV cure-focused science. J Virus Erad. 2020;6(4):100018.

Armstrong R, Hall BJ, Doyle J, Waters E. “Scoping the scope” of a cochrane review. J Public Health (Oxf). 2011;33(1):147–50.

Tricco AC, Lillie E, Zarin W, O’Brien KK, Colquhoun H, Levac D, et al. PRISMA extension for scoping reviews (PRISMA-ScR): checklist and explanation. Ann Intern Med. 2018;169(7):467–73.

Peterson C, Kiem H. Cell and gene therapy for HIV cure. Curr Trop Microbiol Immunol. 2018;417:211–8.

DiGiusto DL, Stan R, Krishnan A, Li H, Rossi JJ, Zaia JA. Development of hematopoietic stem cell based gene therapy for HIV-1 infection: considerations for proof of concept studies and translation to standard medical practice. Viruses. 2013;5(11):2898–919.

Ward AR, Mota TM, Jones RB. Immunological approaches to HIV cure. Semin Immunol. 2020. https://doi.org/10.1016/j.smim.2020.101412 .

Carcelain G, Autran B. Immune interventions in HIV infection. Immunol Rev. 2013;254(1):355–71.

Ananworanich J, Dubé K, Chomont N. How does the timing of antiretroviral therapy initiation in acute infection affect HIV reservoirs? Curr Opin HIV AIDS. 2015;10(1):18–28.

Margolis DM, Garcia JV, Hazuda DJ, Haynes BF. Latency reversal and viral clearance to cure HIV-1. Science. 2016;353(6297):aaf6517.

Archin N, Sung J, Garrido C, Soriano-Sarabia N, Margolis D. Eradicating HIV-1 Infection: Seeking to Clear a Persistent Pathogen. Nat Rev Microbiol. 2014;12(11):750–64.

Dubé K, Sylla L, Dee L, Taylor J, Evans D, Bruton C, et al. Research on HIV cure: mapping the ethics landscape. PLoS Med. 2017;14(12):e1002470.

Sugarman J, Lewin SR, Henrich TJ, Rasmussen T. Ethics of ART interruption after stem-cell transplantation. Lancet HIV. 2016;3(1):e8-10.

Stan R, Zaia JA. Practical considerations in gene therapy for HIV cure. Curr HIV/AIDS Rep. 2014;11(1):11–9.

Margolis DM, Hazuda DJ. Combined approaches for HIV cure. Curr Opin HIV AIDS. 2013;8(3):230–5.

Schwarzer R, Gramatica A, Greene WC. Reduce and control: a combinatorial strategy for achieving sustained HIV remissions in the absence of antiretroviral therapy. Viruses. 2019;12(188):1–31.

Ananworanich J, Barré-Sinoussi F. Is it time to abandon single intervention Cure Trials? Lancet HIV. 2015;2(10):e410–1.

Lebbink RJ, Jong DCM De, Wolters F, Kruse EM, Ham PM Van, Wiertz EJHJ, et al. A Combinational CRISPR/Cas9 Gene-Editing Approach Can Halt HIV Replication and Prevent Viral Escape. Nat Publ Gr. 2017;(December 2016):1–10.

Ho Y-C, Siliciano JD. Efforts to eliminate the latent reservoir in resting CD4+ T cells: strategies for curing HIV-1 infection. J Virus Erad. 2015;1(4):229.

Autran B. Toward a cure for HIV: seeking effective therapeutic vaccine strategies. Eur J Immunol. 2015;45(12):3215–21.

Halper-Stromberg A, Lu CL, Klein F, Horwitz JA, Bournazos S, Nogueira L, et al. Broadly neutralizing antibodies and viral inducers decrease rebound from HIV-1 latent reservoirs in humanized mice. Cell. 2014;158(5):989–99.

Margolis DM, Koup RA, Ferrari G. HIV antibodies for treatment of HIV infection. Immunol Rev. 2017;275(1):313–23.

UCSD. Last Gift. A University of California San Diego Study. [Internet]. 2018. Available from: http://lastgift.ucsd.edu/

Dubé K, Gianella S, Concha-Garcia S, Little SJ, Kaytes A, Taylor J, et al. Ethical considerations for HIV cure-related research at the end of life. BMC Med Ethics. 2018;19(83):1–16.

Gianella S, Taylor J, Brown TR, Kaytes A, Achim CL, Moore DJ, et al. Can Research at the end of life be a useful tool to advance HIV cure? AIDS. 2017;31:1–4.

Chaillon A, Gianella S, Dellicour S, Rawlings SA, Schlub TE, de Oliveira MF, et al. HIV persists throughout deep tissues with repopulation from multiple anatomical sources. J Clin Invest. 2020;130(4):1699–712.

Pentz RD, Cohen CB, Wicclair M, Devita MA, Flamm AL, Youngner SJ, et al. Ethics guidelines for research with the recently dead. Nat Med. 2005;11(11):1145–9.

Dubé K, Patel H, Concha-Garcia S, Nathan A, Miller B, Kaytes A, et al. Perceptions of next-of-kin/loved ones about last gift study participation at the end of life. Strategies for an HIV Cure. 2018;36(12):1033–46.

Dubé K, Patel H, Concha-Garcia S, Perry KE, Mathur K, Javadi S, et al. Perceptions of next-of-Kin/loved ones about last gift rapid research autopsy study enrolling people with HIV/AIDS at the end-of-life: a qualitative interview study. AIDS Res Hum Retroviruses. 2020;36(12):1033–46.

Javadi SS, Mathur K, Concha-Garcia S, Patel H, Perry K, Lo M, et al. Attitudes and perceptions of next-of-Kin/loved ones toward end-of-life HIV cure-related research: a qualitative focus group study in Southern California. PLoS ONE. 2021;16(5):e0250882.

Prakash K, Gianella S, Dubé K, Taylor J, Lee G, Smith D. Willingness to participate in HIV research at the end of life (EOL). PLoS ONE. 2018;13(7):e0199670.

Brown R, Evans NG. The social value of candidate HIV cures: actualism versus possibilism. J Med Ethics. 2017;43(1):118–23.

Lewin SR, Attoye T, Bansbach C, Doehle B, Dube K, Dybul M, et al. Multi-stakeholder consensus on a target product profile for an HIV cure. Lancet HIV. 2021;8(1):e42-50.

Sugarman J. Ethics of HIV and hepatitis B cure research. Curr Opin HIV AIDS. 2020;15(3):1–5.

Joffe S, Miller FG. Bench to bedside. mapping the moral terrain of clinical research. Hastings Cent Rep. 2008;38(2):30–42.

Beacroft L, Hallett T. The potential impact of a “curative intervention” for HIV: a modeling study. Glob Health Res Policy. 2019;4:2. https://doi.org/10.1186/s41256-019-0107-1 .

Dubé K, Auerbach JD, Stirratt MJ, Gaist P. Applying the behavioural and social sciences research (BSSR) functional framework to HIV cure research. J Int AIDS Soc. 2019;22:e25404.

Emanuel EJ, Wendler D, Killen J, Grady C. What makes clinical research in developing countries ethical? The benchmarks of ethical research. J Infect Dis. 2004;189:930–7.

Pitler L. Ethics of AIDS clinical trials in developing countries: a review. Food Drug Law J. 2016;57:133–53.

Moodley K, Rossouw T, Staunton C, Colvin CJ. Synergies, tensions and challenges in HIV prevention, treatment and cure research: exploratory conversations with HIV experts in South Africa. BMC Med Ethics. 2016;17(1):26.

Henderson GE, Peay HL, Kroon E, Cadigan RJ, Meagher K, Jupimai T, et al. Ethics of treatment interruption trials in HIV cure research: addressing the conundrum of risk/benefit assessment. J Med Ethics. 2018;44(4):270–6.

Dubé K, Evans D, Dee L, Sylla L, Taylor J, Weiner BJ, et al. “We need to deploy them very thoughtfully and carefully”: perceptions of analytical treatment interruptions in HIV cure research in the United States. AIDS Res Hum Retroviruses. 2017;34(1):67–79.

Garner SA, Rennie S, Ananworanich J, Dubé K, Margolis DM, Sugarman J, et al. Interrupting antiretroviral treatment in HIV cure research: scientific and ethical considerations. J Virus Erad. 2017;3:82–4.

Lelièvre JD, Hocqueloux L. Unintended HIV-1 transmission to a sex partner in a study of a therapeutic vaccine candidate. J Infect Dis. 2019;220(Suppl 1):S5–6.

Palich R, Ghosn J, Chaillon A, Delobel P, Molina J, Thiebaut R, et al. Viral rebound in semen after antiretroviral treatment interruption in an HIV therapeutic vaccine double-blind trial. AIDS. 2019;33(2):279–84.

Dee L, Boone CA, Palm D, Campbell D, Dubé K. Secondary HIV infection and mitigation in cure-related HIV trials during analytical treatment interruptions. J Infect Dis. 2019;220(7):34–7.

Power J, Westle A, Dowsett GW, Lucke J, Tucker JD, Sugarman J, et al. Perceptions of HIV cure research among people living with HIV in Australia. PLoS ONE. 2018;13(8):e0202647.

Power J, Dowsett GW, Westle A, Tucker JD, Hill S, Sugarman J, et al. The Significance and expectations of HIV cure research among people living with HIV in Australia. PLoS ONE. 2020;15(3):e0229733.

Grace D, Chown SA, Kwag M, Steinberg M, Lim E, Gilbert M, et al. Becoming “Undetectable”: longitudinal narratives of Gay Men’s sex lives after a recent HIV diagnosis. AIDS Educ Prev. 2015;27(4):333–49.

Dubé K, Kanazawa JT, Dee L, Taylor J, Campbell DM, Brown BJ, et al. Ethical and practical considrations for mitigating risks to sexual partners during analytical treatment interruptions in HIV cure-related reserch. HIV Res Clin Pract. 2021;22(1):1–17.

Sugarman J. Ethical considerations regarding oral preexposure prophylaxis in HIV prevention trials. Curr Opin HIV AIDS. 2016;11(1):109–15.

Sugarman J, Celum C, Donnell D, Mayer K. Ethical considerations for new HIV prevention trials. Lancet. 2019;6(August):e489–91.

Grimsrud A, Wilkinson L, Eshun-Wilson I, Holmes C, Sikazwe I, Eshun-wilson I. Understanding engagement in HIV programmes: how health services can adapt to ensure no one is left behind. Curr HIV/AIDS Rep. 2020;15(5):458–66.

Namazi G, Fajnzylber JM, Aga E, Bosch RJ, Acosta EP, Sharaf R, et al. The control of HIV after antiretroviral medication pause (CHAMP) study: posttreatment controllers identified from 14 clinical studies. J Infect Dis. 2018;218(12):1954–63.

Lau JSY, Smith MZ, Allan B, Martinez C, Power J, Lewin SR, et al. Perspectives on analytical treatment interruptions in people living with HIV and their health care providers in the landscape of HIV cure-focused studies. AIDS Res Hum Retroviruses. 2019;36(4):1–8.

Curno MJ, Rossi S, Hodges-Mameletzis I, Johnston R, Price MA, Heidari S. A Systematic review of the inclusion (or exclusion) of women in HIV research: from clinical studies of antiretrovirals and vaccines to cure strategies. JAIDS. 2016;71(2):181–8.

Poteat T, Aqil A, Corbett D, Evans D, Dubé K. “I would really want to know that they had my back”: Transgender Women’s Perceptions of HIV Cure-Related Research in the United States. PLoS ONE. 2020;15(12):e0244490.

Dubé K, Kanazawa JT, Campbell C, Boone CA, Maragh-Bass A, Campbell DM, et al. Considerations for increasing racial, ethnic, gender and sexual diversity in HIV cure-related research with analytical treatment interruptions: a qualitative inquiry. AIDS Res Hum Retroviruses. 2021. https://doi.org/10.1089/AID.2021.0023 .

Kimmelman J, London AJ. Predicting harms and benefits in translational trials: ethics, evidence, and uncertainty. PLoS Med. 2011;8(3):1–5.

Chapman AR. Addressing the ethical challenges of first-in-human trials. J Clin Res Bioeth. 2011;2(4):1–8.

Dubé K, Perry K, Mathur K, Lo M, Javadi S, Patel H, et al. Altruism: scoping review of the literature and future directions for HIV cure-related research. J Virus Erad. 2020;6(4):100008.

Jansen L. The ethics of altruism in clinical research. Hastings Cent Rep. 2009;39(4):26–36.

Eyal N. The benefit/risk ratio challenge in clinical research, and the case of HIV cure: an introduction. J Med Ethics. 2017;43:100–3.

Buchak L. Why High-Risk, Non-expected utility maximising gambles can be rational and beneficial: the case of HIV cure studies. J Med Ethics. 2016;43(2):1–6.

Rid A, Wendler D. A framework for risk-benefit evaluations in biomedical research. Kennedy Inst Ethics J. 2011;21(2):141–79.

Wikler D. Must research benefit human subjects if it is to be permissible? J Med Ethics. 2017;43(2):114–7.

Aarons DE. Exploring the risk/benefit balance in biomedical research: some considerations. Rev Bioét. 2017;25(2):320–7.

Eyal N, Kuritzkes DR. Challenges in clinical trial design for HIV-1 cure research. Lancet. 2013;382(9903):1464–5.

Różyńska J. On the alleged right to participate in high-risk research. Bioethics. 2015;29(7):451–61.

Weijer C. Thinking clearly about research risk: implications of the work of Benjamin Freedman. IRB. 1999;21(6):1–5.

Steel R. Reconceptualising risk—benefit analyses: the case of HIV cure research. J Med Ethics. 2020;46(3):212–9.

Eyal N. How to keep high-risk studies ethical: classifying candidate solutions. J Med Ethics. 2017;43(2):74–7.

Largent E. For love and money: the need to rethink benefits in HIV cure studies. J Med Ethics. 2017;43(2):96–9.

Evans D. An activist’s argument that participant values should guide risk-benefit ratio calculations in HIV cure research. J Med Ethics. 2017;43(2):100–3.

Mehraj V, Ghali P, Ramendra R, Costiniuk C, Lebouché B, Ponte R, et al. The evaluation of risk-benefit ratio for gut tissue sampling in HIV cure research. J Virus Erad. 2017;3:212–7.

Allers K, Hütter G, Hofmann J, Loddenkemper C, Rieger K, Thiel E, et al. Evidence for the cure of HIV infection by CCR5Δ32/Δ32 stem cell transplantation. Blood. 2011;117(10):2791–9.

Gupta RK, Abdul-Jawad S, McCoy LE, Mok HP, Peppa D, Salgado M, et al. HIV-1 remission following CCR5 ∆-32/∆-32 haematopoietic stem-cell transplantation. Nature. 2019;568(7751):244–8.

Peay H, Ormsby N, Henderson G, Jupimai T, Rennie S, Siripassorn K, et al. Recommendations from Thai Stakeholders about Protecting HIV Remission ('Cure’) Trial Participants: Report from a Participatory Workshop. Int Health. 2020;12:567–74.

Peluso MJ, Dee L, Shao S, Taylor J, Campbell D, Collins S, et al. Operationalizing HIV cure-related trials with analytic treatment interruptions during the SARS-Cov-2 pandemic: a collaborative approach. Clin Infect Dis. 2020;72(10):ciaa1260.

Peluso MJ, Dee L, Taylor J, Campbell D, Ehm A, Agosto-Rosario M, et al. SARS-Cov-2 vaccination in the context of ongoing HIV cure-related studies. J Acquir Immune Defic Syndr. 2021;84(4):e232–2.

Stecher M, Klein F, Lehmann C, Platten M, Gillor D, Behrens G, et al. Systematic review of the current literature on structured treatment interruptions in HIV-infected patients receiving ART: implications for HIV cure trials. Clin Infect Dis. 2020;70(7):1406–17.

Lau JSY, Smith MZ, Lewin SR, McMahon JH. Clinical trials of antiretroviral treatment interruption in HIV-infected individuals. AIDS. 2019;33:773–91.

Dubé K, Hosey L, Starr K, Evans D, Hoffman E, Campbell D, et al. Participant Perspectives in an HIV cure-related trial conducted exclusively in women in the United States: Results from AIDS Clinical Trials Group (ACTG) 5366. AIDS Res Hum Retroviruses. 2020;36(4):268–82.

Perry KE, Dubé K, Concha-Garcia S, Patel H, Kaytes A, Taylor J, et al. "My Death Will Not [Be] in Vain: Testimonials from Last Gift Rapid Research Study Participants Living with HIV at the End of Life. AIDS Res Hum Retroviruses. 2020;36(12):1071–82.

Diepstra KL, Barr L, Palm D, Hogg E, Mollan KR, Henley L, et al. Participant perspectives and experiences entering an intensively monitored antiretroviral pause: results from the AIDS clinical trials group A5345 biomarker study. AIDS Res Hum Retroviruses. 2021;37(6):489–501.

Freshwater W. From early AIDS vaccine to HIV cure research with analytical treatment interruption trials: a study participant testimonial. J Virus Erad. 2019;5(4):231–3.

Hawley C. “Fear overcome by love”: why I participated in HIV cure research. J Virus Erad. 2018;4:248–9.

Brown TR. I Am the Berlin patient: a personal reflection. AIDS Res Hum Retroviruses. 2015;31(1):2–3.

Protière C, Arnold M, Fiorentino M, Fressard L, Leli JD, Mora M, et al. Differences in HIV cure clinical trial preferences of French people living with HIV and physicians in the ANRS-APSEC study: a discrete choice experiment. J Int AIDS Soc. 2020;23(e25443):1–9.

Shah SK. When to start paediatric testing of the adult HIV cure research agenda? J Med Ethics. 2017;43(2):82–6.

Griffith D, Agwu A. Caring for youth living with HIV across the continuum: turning gaps into opportunities. AIDS Care. 2017;29:1205–11.

Shah SK, Persaud D, Wendler DS, Taylor H, Gay H, Kruger M, et al. Research into a functional cure for HIV in neonates: the need for ethical foresight. Lancet Infect Dis. 2014;14(9):893–8.

Dubé K, Henderson GE, Margolis DM. Framing expectations in early HIV cure research. Trends Microbiol. 2014;22(10):547–9.

Tucker J, Volberding P, Margolis D, Rennie S, Barré-Sinoussi F. Words matter: discussing research towards an HIV cure in research and clinical contexts. JAIDS J Acquir Immune Defic Syndr. 2014;67(3):110–1.

Rennie S, Siedner M, Tucker JD, Moodley K. The ethics of talking about “HIV cure.” BMC Med Ethics. 2015;16:18.

Nie J-B, Gilbertson A, de Malcolm R, Staunton C, van Niekerk A, Tucker JD, et al. Healing without waging war: beyond military metaphors in medicine and HIV cure research. Am J Bioeth. 2016;16(10):3–11.

Dubé K, Luter S, Lesnar B, Newton L, Galea J, Brown B, et al. Use of “eradication” in HIV cure-related research: a public health debate. BMC Public Health. 2018;18:245.

Newton L, Necochea R, Palm D, Taylor J, Barr L, Patel H, et al. Revisiting the “sterilizing cure” terminology: a call for more patient-centred perspectives on HIV cure-related research. J Virus Erad. 2019;5(2):122–4.

Dubé K, Willenberg L, Dee L, Sylla L, Taylor J, Roebuck C, et al. Re-examining the HIV ‘functional cure’ oxymoron: time for precise terminology? J Virus Erad. 2020;6(October):100017.

Bromley E, Mikesell L, Jones F, Khodyakov D. From subject to participant: ethics and the evolving role of community in health research. Am J Public Health. 2015;105(5):900–8.

DAIDS. NIAID Language Guide [Internet]. 2020. p. 25. Available from: https://daidslearningportal.niaid.nih.gov/local/pages/?id=17

Dilmitis S, Edwards O, Hull B, Margolese S, Mason N, Namiba A, et al. Language, identity and HIV: why do we keep talking about the responsible and responsive use of language? Lang Matters JIAS. 2012;15(Suppl 2):2–4.

Annas GJ. Cure research and consent: the Mississippi Baby, Barney Clark, Baby Fae, and Martin Delaney. J Med Ethics. 2017;43:104–7.

Henderson GE, Waltz M, Meagher K, Cadigan RJ, Jupimai T, Phanuphak N, et al. Going off antiretroviral treatment in a closely monitored HIV “cure” trial: longitudinal assessments of acutely diagnosed trial participants and decliners. J Int. 2019;22:e25260.

Henderson GE, Rennie S, Corneli A, Peay HL. Cohorts as collections of bodies and communities of persons: insights from the SEARCH010/RV254 research cohort. Int Health. 2020;12:584–90.

Horng S, Grady C. Misunderstanding in clinical research: distinguishing therapeutic misconception, therapeutic misestimation, and therapeutic optimism. IRB. 2003;25(1):11–6.

Miller FG, Brody H. A critique of clinical equipoise. Therapeutic misconception in the ethics of clinical trials. Hastings Cent Rep. 2003;33(3):19–28.

Weinfurt KP, Seils DM, Tzeng JP, Compton KL, Sulmasy DP, Astrow AB, et al. Expectations of benefit in early-phase clinical trials: implications for assessing the adequacy of informed consent. Med Decis Mak. 2008;28(4):575–81.

Staunton C. Informed consent for HIV cure research in South Africa: issues to consider. BMC Med Ethics. 2015;16:3. https://doi.org/10.1186/1472-6939-16-3 .

Moodley K, Staunton C, Rossouw T, De Roubaix M, Duby Z. The psychology of “cure”. Unique challenges to consent processes in HIV cure research in South Africa. BMC Med Ethics. 2019;20(9):1–11.

Pan X, Zhang A, Henderson GE, Rennie S, Liu C, Cai W, et al. Traditional, Complementary, and alternative medical cures for HIV: rationale and implications for HIV cure research. Glob Public Health. 2019;14(1):152–60.

Protière C, Fressard L, Mora M, Meyer L, Preau M, Suzan-Monti M, et al. Characterization of physicians that might be reluctant to propose HIV cure-related clinical trials with treatment interruption to their patients? The ANRS-APSEC Study. Vaccines. 2020;8:334.

Lau JS, Smith M, Allan B, Martinez C, Power J, Lewin S, et al. Acceptability, motivation and the prospect of cure for people living with HIV and their healthcare providers in HIV cure-focused treatment interruption studies. AIDS Res Ther. 2020;17(65):1–6.

Brion J. The patient-provider relationship as experienced by a diverse sample of highly adherent HIV-infected people. J Assoc Nurses AIDS Care. 2014;25(2):123–34.

Sugarman J, Lavori PW, Boegerfd M, Cainb C, Edson R, Morrisonf V, et al. Evaluating the quality of informed consent. Clin Trials. 2005;2:34–41.

Lavori PW, Wilt TJ, Sugarman J. Quality assurance questionnaire for professionals fails to improve the quality of informed consent. Clin Trials. 2007;4:638–49.

Sauceda JA, Dubé K, Brown B, Pérez AE, Rivas CE, Evans D, et al. Framing a consent form to improve consent understanding and determine how this affects willingness to participate in HIV cure research : an experimental survey study. J Empir Res Hum Res Ethic. 2020;16(1–2):78–87.

Dhilbegovic B. Uncertainty and equipoise: at interplay between epistemology, decision-making and ethics. Am J Med Sci. 2011;342(4):282–9.

IOM. Characterizing Uncertainty in the Assessment of Benefits and Risks of Pharmaceutical Products—Workshop in Brief. 2017.

Beauchamp T, Childress J. Principles of biomedical ethics. 3rd ed. Oxford: Oxford University Press; 1989. p. 470.

Emanuel EJ, Wendler D, Grady C. What makes clinical research ethical? JAMA J Am Med Assoc. 2013;283(20):2701–11.

Henrich TJ, Hanhauser E, Marty FM, Sirignano MN, Keating S, Lee T-H, et al. Antiretroviral-free HIV-1 remission and viral rebound after allogeneic stem cell transplantation: report of 2 cases. Ann Intern Med. 2014;161(5):319–27.

Henrich TJ, Hanhauser E, Sirignano MN, Li JZ, Lichterfeld M, Marty FM, et al. HIV-1 Rebound following allogeneic stem cell transplantation and treatment interruption. In: CROI. 2014.

Persaud D, Gay H, Ziemniak C, Chen YH, Piatak M, Chun T-W, et al. Absence of detectable HIV-1 viremia after treatment cessation in an infant. N Engl J Med. 2013;369(19):1828–35.

Luzuriaga K, Gay H, Siemniak C, Sanborn KB, Somasundaran M, Rainwater-Lovett K, et al. Viremic relapse after HIV-1 remission in a perinatally infected child. N Engl J Med. 2015;372(8):784–6.

Deakin CT, Alexander IE, Hooker CA, Kerridge IH. Gene therapy researchers’ assessments of risks and perceptions of risk acceptability in clinical trials. Mol Ther. 2013;21(4):806–15.

Dubé K, Barr L, Palm D, Brown B, Taylor J. Putting Participants at the Centre of HIV Cure Research. Lancet HIV. 2019;3018(19):18–9.

FDA. Patient Preference Information - Voluntary Submission, Review in Premarket Approval Applications, Humanitarian Device Exemption, Applications, and De Novo Requests, and Inclusion in Decision Summaries and Device Labeling. 2016.

FDA. The Voice of the Patient. 2014.

Protière C, Spire B, Mora M, Poizot-Martin I, Doumergue M, Morlat P, et al. Patterns of patient and healthcare provider viewpoints regarding participation in HIV cure-related clinical trials. Findings from a Multicentre French Survey Using Q Methodology (ANRS-ASPECT). PLoS ONE. 2017;12(11):e0187489.

Dubé K, Eskaf S, Evans D, Sauceda J, Saberi P, Brown B, et al. The dose response: perceptions of people living with HIV in the United States on alternatives to oral daily antiretroviral therapy. AIDS Res Hum Retroviruses. 2019;36(4):324–48.

Dubé K, Campbell DM, Perry KE, Kanazawa JT, Saberi P, Sauceda JA, et al. Reasons people living with HIV might prefer oral daily antiretroviral therapy, long-acting formulations, or future HIV remission options. AIDS Res Hum Retroviruses. 2020;36(12):1054–8.

Safreed-Harmon K, Anderson J, Azzopardi-muscat N, Behrens GMN, Monforte A, Davidovich U, et al. Reorienting health systems to care for people with HIV beyond viral suppression. Lancet HIV. 2019;6(12):e869–77.

Peay H, Henderson G. What motivates participation in HIV cure trials? A call for real-time assessment to improve informed consent. J Virus Erad. 2015;1(1):51–3.

Dubé K, Simoni J, Louella M, Sylla L, Mohamed ZH, Patel H, et al. Acceptability of cell and gene therapy for curing HIV infection among people living with HIV in the Northwestern United States: a qualitative study. AIDS Res Hum Retroviruses. 2019;35(7):649–59.

Lo Y, Chu C, Ananworanich J, Excler J, Tucker JD. Stakeholder engagement in HIV cure eesearch: lessons learned from other HIV interventions and the way forward. AIDS Patient Care STDS. 2015;29(7):1–11.

UNAIDS, AVAC. Good Participatory Practice Guidelines for Biomedical HIV.

CPTR. Good Participatory Practice Guidelines for TB Drug Trials. 2012.

WHO. Good Participatory Practice Guidelines for Trials of Emerging (and Re-Emerging) Pathogens That Are Likely to Cause Severe Outbreaks in the Near Future and For Which Few or No Medical Countermeasures Exist (GPP-EP). 2016.

Shippee ND, Domecq Garces JP, Prutsky Lopez GJ, Wang Z, Elraiyah TA, Nabhan M, et al. Patient and service user engagement in research: a systematic review and synthesized framework. Heal Expect. 2015;18(5):1151–66.

Kottow MH. Clinical and research ethics as moral strangers. Arch Immunol Ther Exp (Warsz). 2009;57(3):157–64.

Download references

Acknowledgements

The authors would like to thank the AntiViral Research Center (AVRC) Community Advisory Board (CAB), the AIDS Clinical Trials Group (ACTG) Community Scientific Sub-Committee (CSS), the amfAR Institute for HIV Cure Research CAB, the Martin Delaney Collaboratories Towards an HIV-1 Cure CABs—in particular the Delaney AIDS Research Enterprise (DARE) CAB, the BEAT-HIV Collaboratory CAB, and the defeatHIV CAB. We are most grateful to all PLWH who inspire this work every day.

This work was supported by an Ethics Administrative Supplement to R21MH118120 to K.D. and by R21MH122280 to P.S. and K.D. Funders had no role in the design of the study, data collection and analysis, interpretation of the data and writing of the manuscript.

Author information

Authors and affiliations.

University of North Carolina at Chapel Hill, Gillings School of Global Public Health, 4108 McGavran-Greenberg Hall, Chapel Hill, NC, 27599-7469, USA

Karine Dubé, John Kanazawa, Hursch Patel, Samuel Ndukwe & Laney Henley

HIV + Aging Research Project – Palm Springs (HARP–PS), Palm Springs, CA, USA

Jeff Taylor

AntiViral Research Center (AVRC) Community Advisory Board (CAB), San Diego, CA, USA

Collaboratory of AIDS Researchers for Eradication (CARE) CAB, Chapel Hill, NC, USA

Jeff Taylor & David Palm

AIDS Action Baltimore, Baltimore, MD, USA

Delaney AIDS Research Enterprise (DARE) Community Advisory Board (CAB), San Francisco, CA, USA

Lynda Dee & Danielle M. Campbell

BEAT-HIV Collaboratory CAB, Philadelphia, PA, USA

Nora Jones & Christopher Roebuck

defeatHIV CAB, Seattle, WA, USA

Laurie Sylla & Michael Louella

AIDS Clinical Trials Group (ACTG) Community Scientific Subcommittee (CSS) Ethics Working Group, Nationwide, USA

Jan Kosmyna, David Kelly & Morénike Giwa Onaiwu

AIDS Clinical Trials Group Global CAB, Washington, D.C., USA

Orbit Clanton

Institute of Global Health and Infectious Diseases HIV Treatment and Prevention CAB, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Charles R. Drew College of Medicine and Science, Los Angeles, CA, USA

Danielle M. Campbell

Center for the Study of Women, Gender, and Sexuality (School of Humanities), Rice University, Houston, TX, USA

Morénike Giwa Onaiwu

Center for AIDS Prevention Studies (CAPS), Division of Prevention Sciences, UCSF, San Francisco, CA, USA

Mallory O. Johnson, Parya Saberi & John A. Sauceda

Department of Social Medicine, Population and Public Health, Center for Healthy Communities, University of California, Riverside, Riverside, CA, USA

Brandon Brown

Johns Hopkins Berman Institute for Bioethics, Baltimore, MD, USA

Jeremy Sugarman

You can also search for this author in PubMed   Google Scholar

Contributions

K.D. drafted the initial version of this manuscript. J.K., J.T., L.D., N.J., C.R., L.S., M.L., J.K., D.K., O.C., D.P., D.M.C., M.G.O., H.P., H.P., S.N., L.H., M.O., P.S., B.B., J.A.S., J.S. reviewed the manuscript for intellectual contents. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Karine Dubé .

Ethics declarations

Ethics approval and consent to participate.

Not applicable. This manuscript did not involve human participants, human data, or human tissue.

Consent for publication

Not applicable. This manuscript does not contain any individual person’s data not contained in the peer-reviewed literature.

Competing interests

Jeremy Sugarman is a member of Merck KGaA’s Bioethics Advisory Panel and Stem Cell Research Oversight Committee; a member of IQVIA’s Ethics Advisory Panel; a member of Aspen Neurosciences Scientific Advisory Board; a member of a Merck Data Monitoring Committee; a consultant to Biogen; and a consultant to Portola Pharmaceuticals Inc. None of these activities are related to the material discussed in this manuscript. No other authors have outside interests to declare.

Additional information

Publisher's note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ . The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Cite this article.

Dubé, K., Kanazawa, J., Taylor, J. et al. Ethics of HIV cure research: an unfinished agenda. BMC Med Ethics 22 , 83 (2021). https://doi.org/10.1186/s12910-021-00651-1

Download citation

Received : 09 December 2020

Accepted : 23 June 2021

Published : 30 June 2021

DOI : https://doi.org/10.1186/s12910-021-00651-1

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

  • HIV cure research
  • Research ethics
  • Experimental medicine

BMC Medical Ethics

ISSN: 1472-6939

research paper on hiv/aids

  • Open access
  • Published: 13 February 2024

Disruptions to HIV services due to the COVID pandemic in the USA: a state-level stakeholder perspective

  • Rogério M. Pinto 1 ,
  • Evan Hall 1 ,
  • Vitalis Im 1 ,
  • Carol A. Lee 2 &
  • Sunggeun (Ethan) Park 1  

BMC Health Services Research volume  24 , Article number:  196 ( 2024 ) Cite this article

210 Accesses

Metrics details

The United States envisions a 90% reduction in HIV infections by 2030. However, the COVID-19 pandemic disrupted the HIV continuum and disproportionately affected access to social and health services for people at the highest vulnerability. This study shows how stakeholders in the State of Michigan handled disruptions and their key recommendations. As a case study, this study adds to the literature about preparedness for future pandemics.

We interviewed 33 statewide Michigan HIV/AIDS Council members—practitioners, researchers, and community representatives, guiding service planning, improvement, and resource allocations, measuring group cohesiveness using a tested scale. We measured group cohesiveness as a proxy for how individual opinions reflected those of the Council as a group. We used qualitative questions to assess: (1) how the COVID-19 pandemic disrupted HIV prevention; (2) how disruptions were handled; and (3) recommendation to help address disruptions now and in the future. Using thematic analysis, we coded the interviews.

We found a high degree of cohesiveness. Participants agreed that the pandemic disrupted HIV prevention services (e.g., HIV testing, PrEP education, referrals to primary care, etcetera) offered by community organizations, hospital clinics, and health departments across the state. In response, they developed online and curbside services to maintain HIV services, abate social isolation, and address structural issues like lack of food and public transportation. We organized results in four categories: (1) HIV service disruptions (e.g., “ Housing for women and children who are fleeing a legal situation ”); (2) Responses to disruptions (e.g., “S ome of them, we would say, hey, weather permitting, we’ll come out to your car ”); (3) Minoritized groups disproportionately affected (e.g., “ Especially in my community, to get people if there’s ever a vaccine, Black people are going to be the last people to take it ”); and (4) Recommendations (below).

Conclusions

The pandemic unsettled and further exacerbated every aspect of HIV service provision. The main recommendation was to overhaul communication systems between government and organizations offering HIV services to mitigate disruptions and improve the chances of achieving a 90% reduction.

Peer Review reports

Introduction

The United States (U.S.) envisions a 90% reduction in HIV infections by the end of this decade [ 1 ]. However, the COVID-19 pandemic severely and unprecedently disrupted the lives and work of people across the globe [ 2 , 3 ], including their health, stress, and life satisfaction. More specifically, the pandemic disrupted the HIV Continuum of Prevention and Care (“HIV continuum”), which connects people living with HIV (PLWH) and high-vulnerability individuals to appropriate prevention and care services, including HIV testing, pre-exposure prophylaxis (PrEP), and adherence to antiretroviral medications. A burgeoning literature started in early 2020 showing that, across the globe and particularly in the U.S., the pandemic disproportionately affected negatively those most vulnerable to HIV infections. These populations, including, Black, Indigenous, People of Color (BIPOC), men who have sex with men (MSM), people who inject/use drugs (PWID), and transgender and non-binary persons experienced a sudden disconnection from HIV continuum services [ 4 , 5 ]. The initial research was based on rapid atheoretical, data collection and anecdotal accounts of how community-based organizations (CBOs), hospital clinics, and health departments in different geographic locations addressed mounting gaps in services. Currently, we have data on the services that were most disrupted and on how health service providers addressed gaps [ 6 , 7 ].

We submit that the literature connecting the COVID-19 and HIV pandemic needs to expand to include local accounts of how stakeholders handled HIV services vis-à-vis COVID disruptions. The recent pandemic demonstrates how geographic location and geopolitics (e.g., shelter-in-place and shut down orders) influenced disruptions to the HIV services differently, highlighting the importance of documenting locally-based solutions and recommendations for addressing future outbreaks and disruptions. Therefore, following a community-engaged approach to research, we recruited the Michigan HIV/AIDS Council (MHAC)—a collective of practitioners, researchers, and community members across the state of Michigan, guiding the service planning, capacity improvement, and resource allocation decisions of the state for HIV resources and information. This paper explores (1) how the pandemic disrupted the HIV services with an emphasis on health inequities, (2) how HIV-serving organizations and individual providers handled the disruptions, and (3) recommendations made by the Council members.

Impact of COVID on organizations delivering HIV continuum services and their responses

Organizations that deliver HIV services had experienced pre-pandemic matters that challenged their capacities to respond to their clients. Matters affecting organizations are both at the service provider and structural levels, such as not being able to work in the office, shutdowns, staff layoffs, institutional low morale, and fears related to COVID [ 8 ]. Community-based organizations have faced budgetary shortfalls and thus a decrease in overall employment and ability to provide essential services. Research indicates that the pandemic has disrupted both the form and function of disaster preparedness– it affected one’s ability to see people in person, to offer food and services to people required to shelter-in-place, to find volunteers to supplement service provisions, and to allocate funds while maintaining fairness and equity in the distribution of resources across populations [ 9 ].

Organizations providing HIV services implemented existing and novel approaches to HIV service disruptions, including curbside service delivery, telehealth for HIV prevention and treatment service, including PrEP prescription and maintenance [ 10 ]. However, organizations across the U.S. responded to the pandemic disruptions differently. For instance, in March 2020, most Ryan White-funded clinics in South Carolina reported partial or complete interruptions to their clinic operations hours, HIV services coverage, telehealth use, and healthcare providers’ availability. Nevertheless, these clinics reported the continuation of core HIV services, such as medication filling and testing, but stopped face-to-face counseling and social support groups. Contrastingly, Ryan White-funded clinics in Alabama suspended walk-in HIV/STI testing and community outreach events. Still, all other services (e.g., legal services, support groups, nutritional services, transportation vouchers, medical items, pet food, and personal care items) were provided through curbside services [ 6 ].

HIV continuum disruptions and impact on key populations

The groups most affected by HIV had already been experiencing multiple personal and structural issues that the COVID pandemic further exacerbated. For example, MSM had faced challenges concerning food insecurity and housing stability before the pandemic [ 11 ]. Hepatitis C and HIV infection rates among PWID had been reduced during COVID, partly because of the increased availability of syringe service programs. However, given disruptions in services, it is still a bit too soon to know whether this reduction will be maintained now and, in the future [ 12 ]. Transgender and non-binary persons experienced job insecurity, unemployment, housing instability, and lack of health insurance prior to the pandemic [ 13 ]. There is little published research thus far on the impact of the COVID pandemic on these vulnerable populations at the intersection of HIV.

COVID-19 further aggravated these vulnerable populations’ prior conditions and ability to access HIV continuum services due to myriad changes in day-to-day domestic life, community life, or life outside of work, including childcare, caring for family members, own healthcare, food scarcity, among others [ 14 ]. As consequences, for example, research on MSM shows changes in sexual behavior, including an increase in the number of sexual partners, thus necessitating an increase in HIV prevention services during the pandemic [ 11 ]. Although there was a desired willingness among MSM to get tested for HIV and PrEP prescription/refills, access to prevention services was difficult for many [ 15 , 16 ]. Similar barriers to HIV care and treatment were concurrent. MSM youth showed decreased condom usage and increased alcohol and/or substance use [ 17 ]. Therefore, there was a need for HIV services to remain open during the pandemic. Due to added demands on healthcare systems, HIV prevention programs, such as syringe exchange, were strained and even suspended [ 12 ]. Other services that became difficult to access included HIV testing, safe-use injecting equipment, and scheduling appointments with doctors and HIV counselors [ 18 ]. Adherence to antiretroviral regimens for people who inject/use drugs decreased during the pandemic alongside and a lack of optimism that PrEP was a viable prevention tool [ 19 ]. It has also been documented that, during the pandemic, transgender and non-binary individuals had less medical attention compared to pre-pandemic levels. Although there was a need to know one’s HIV status, many described substantial confusion about how to access HIV testing and other prevention services [ 13 , 20 ].

Michigan HIV/AIDS council (MHAC) as collaborative governance

By April 2020, our team had published a paper about how MHAC stakeholders forecast major HIV services disruptions at the beginning of the pandemic. Our next step was to adhere to our community-engaged research approach and collect structured interviews and data to shed light on the issues affecting the HIV services [ 21 ]. We specifically chose to work with MHAC as it represents a collaborative governance effort that “brings multiple stakeholders together in common forums with public agencies to engage in consensus-oriented decision making” [ 22 , 23 ]. The goals of collaborative governance efforts, such as MHAC, are often two-fold: normative (e.g., promoting stakeholder involvement and boosting accountability) and outcome-directed (e.g., improving performance on important public policy issues) [ 24 , 25 , 26 ]. The Michigan Department of Health and Human Services (MIDHHS) organizes MHAC “to represent the diversity of those affected by HIV/AIDS in Michigan, maintain collaboration and coordination among prevention and care issues, and develop and sustain statewide comprehensive plans for HIV prevention and care” [ 23 , 27 ]. The MHAC is a deliberative, collaborative governance vehicle to facilitate two-way communications and collaboration channels between private and public stakeholders to improve Michigan’s capacity for services and planning, and to better allocate public resources to improve the HIV continuum. The Council recruits stakeholders representing seven distinctive geographic regions from across the state with various connections to the state’s HIV continuum, including people living with HIV, representatives from AIDS service organizations (e.g., community-based organizations, non-governmental organizations), representatives from local public health agencies, and community members at large. Members serve 3-year terms and commit about 120 h per year to attend meetings and participate in committees and workgroups.

Sampling, recruitment, and data collection

Recruitment and data collection for this study took place approximately between August and December of 2020. The first author introduced the procedures that would be involved in the study during MHAC meetings. After that, our team sent an invitation via email to the entire membership and followed up with individual emails. Two trained research assistants conducted recruitment and the interviews using a Zoom Conferencing System. Interviews lasted between 30 and 60 min. Qualitative interviews were transcribed using Zoom transcriptions; the text for each transcribed interview was “cleaned up” for grammatical errors, missing sentences, and words before data analysis. We also asked the participants to complete the quantitative surveys (about 20 min), including basic demographic characteristics, and roles within the MHAC. In addition, the survey captured the participants’ perspectives and experience with MHAC with validated measures of group cohesion and efficacy. We interviewed 79% of the Council’s membership.

Interview protocol

Semi-structured interview guide.

The guide was based on the topics that had transpired in MHAC meetings when the pandemic was declared and on feedback from our early publication on potential disruptions to HIV services in Michigan and elsewhere [ 21 ]. The protocol included questions and prompts aimed to uncover (1) how the COVID-19 pandemic had disrupted the HIV services; (2) how identified disruptions had been handled; and (3) what actions participants might recommend to help address disruptions now and in the future. First, we asked participants to describe how they thought COVID had disrupted the HIV services. We prompted participants to discuss how COVID might have unearthed health inequities, particularly among people of color. Second, we asked participants to describe how they handled the identified disruptions. The third portion of the interview asked participants to briefly describe what actions they might recommend to help address disruptions now and in the future. Our prompts encouraged participants to discuss disruptions and responses related to the HIV continuum, such as HIV testing, PrEP, and primary care.

Group cohesiveness

We collected the survey data after the qualitative interview using paper and pencil method. We measured group cohesiveness, i.e., agreement on the purpose of MHAC’s mission, as a proxy for how individual opinions reflect those of the Council as a group. Adopted from Dobbins and Zaccaro [ 28 ], i.e., agreement on the purpose of MHAC’s mission, as a proxy for how individual opinions reflected those of the Council as a group. The cohesiveness scale stems from the leadership literature and has been adapted for myriad settings (e.g., business, health care, nursing, criminal justice, military, etc.). Group cohesiveness reflects individuals’ tendency to remain in a group or attachment to the group. Cohesiveness is influenced by group structure, leadership, and satisfaction with group. The measure includes eight statements to which participants provide their level of agreement (1 = Strongly disagree to 7 = strongly agree), such as “The members of MHAC get along well together,” “I enjoy belonging to MHAC because I am friends with many members,” and “I feel that I am really a part of the MHAC.” We calculated descriptive statistics (the mean for each item of the scale) to assess how MHAC members’ opinions and recommendations cohered as a group. We found a high degree of cohesiveness among council members (5.73; SD = 0.57). The lowest mean for any of the seven items on the scale was 5.12 (0.99) (“The members of MHAC will readily defend each other from criticism by outsiders”), and the highest was 6.36 (1.19) (“I find that I generally do not get along with other MHAC members”– reversed).

Analytic approach and data interpretation

Minimizing bias and enhancing trustworthiness.

Before our analysis began, we de-identified all interviews to obscure the names of participants. Each transcript was assigned a new file title. To ensure a maximum degree of “trustworthiness” [ 29 ], we held a weekly debriefing to avoid bias and fatigue. We availed ourselves of our collaboration with MHAC and held member check meetings to add validity to the findings [ 30 ]. Rigor and validation were strengthened using Dedoose, a cross-platform app for storing qualitative data, searching and retrieving text, and linking emerging themes. Because two of the authors were also members of MHAC, this process was particularly important as a deterrent to analysis bias. Their knowledge of the Council’s history, culture, and procedures enhanced data interpretation.

Thematic analysis

We used thematic analysis as the key method for reading, interpreting, and coding textual data. Three coders independently read and developed initial codes using open coding based on three randomly selected interviews. The coders compared their first impressions and initial codes to establish reliability. After feedback from the first author, a coding scheme began to surface. The same procedure was then repeated using another three randomly-chosen interviews and the initial codes for guidance. From this process, a coding scheme was established, which was then used to code the remaining interviews. Though the data were generated from a semi-structured interview, coders were open to finding different ideas, opinions, and observations in the text. Nonetheless, the main goal of the data analysis was to catalog disruptions due to the pandemic, responses to disruptions, and key recommendations. Therefore, we followed a coding scheme closely based on the three protocol questions described above.

Saturation and selecting key findings

We began to see saturation, meaning no new insights were emerging from the data until we had analyzed half of the interviews. Nonetheless, we read all interview transcripts. The results we decided to report reflect the observations and general sensibility of the entire Council. After studying all 33 interviews, an independent research assistant selected ten excerpts marked by the coders and represented the themes of the interview protocol. We used this type of selection criteria for the quotes as another step toward rigor and a way to reduce bias. As a team, we selected what we considered to be the most representative excerpts to be included in this manuscript.

Sample description

Participants have been engaged with MHAC as voting members (sometimes for more than one term) and as volunteers (no-voting members) from less than one to more than 20 years (since its inception). Two of the authors (not interviewed for this study) were MHAC members when the pandemic was declared. The sample included 33 of 44 Michigan HIV/AIDS Council Members (response rate = 79%). The sample includes racially/ethnically diverse respondents— (52% White, 30% Black, 9% multiracial, 6% Latinx, and 3% Asian) with an average age of 42 (range: 19–62). Most participants were female (58%; male = 33%; Other = 9%) and 30% were living with HIV ( N = 10).

HIV services disruptions and how organizations and providers responded

Following the three areas explored in the interviews, we have provided excerpts from different participants. We used quotes that represented the ideas, opinions, and sensibilities of the majority of a council that oversees HIV service provisions in Michigan.

Participants agreed that the pandemic disrupted many services (e.g., HIV testing, PrEP education, referrals to primary care, etcetera) offered by community organizations, hospital clinics, and health departments across the state. Participants explained that the COVID-19 pandemic aggravated issues that pre-dated the pandemic and disproportionately affected minoritized groups. Participants collectively shared their inability to provide the main services that comprise the continuum of care and prevention, including but not limited to HIV testing, PrEP education and referrals to physicians who could prescribe PrEP, and day-to-day provider-client communication between providers and clients, which could help with adherence to HIV medication.

Participants highlighted how COVID affected service providers personally and hindered their ability to maintain the HIV services. One participant talked about competing responsibilities that echoed those of many others.

So, I have a two-year-old, and we were all stuck at home. My husband was also working at this time. So, we really had to maneuver around this. When my 18 [year-old] was stuck home from school… it was arguing with a grown child… about his schooling and stuff, and making sure that he was going to graduate on time, which he didn’t.

Even though service providers, and other stakeholders, had to face personal setbacks, they quickly found creative solutions for making HIV services available under difficult circumstances.

So, I actually created like a time frame for my daughter. What we did was during this time frame. So, when I would put my daughter to bed, this is when I was able to call clients…jot down my notes… everything a client needed at this time.

Participants identified several structural issues that disrupted HIV services—lack of public transportation, housing, food security, and funding insecurity around HIV services for hospitals and community-based health organizations. These issues, which pre-dated the pandemic, greatly affected providers’ ability to bill for rendered services. Similarly, uncertainty about where to send clients for HIV services affected referral-making and thus disrupted the HIV continuum. Being outside of their offices for many months, stakeholders lost connection with clients and colleagues with whom they usually collaborate (e.g., mutual referral-making) to provide HIV services.

You’re not going to come to the doctor, you have no way to get there. Those are issues which have historically been around for as long as I’ve been in this line of work…we have to fix the transportation issue; we have to fix the housing issue.
Housing for women and children who are fleeing a legal situation. So, because of COVID, these women had to be displaced, and they had to leave a safe environment and be put up into a hotel space.
The food bank service category and emergency funds category, and we had to increase those because, as we know, there were a lot of people that lost their jobs.
When this pandemic hit a lot of therapy organizations that, I was looking at, were in crisis mode of writing grants and writing letters to insurance companies as a way to stay afloat. Because a lot of insurances did not cover [pandemic-related services].
The hospital was pretty much hemorrhaging money; we weren’t able to provide any sort of care outside of code… and all those kinds of non-emergent things were put on hold, and that definitely put a little bit of a strain on the system.

Responses to HIV services disruptions

However difficult the impacts of COVID might have been at the personal and/or professional levels, participants identified multiple responses that touched organizations, service providers, and clients alike. These responses, which may have been challenging to service providers and organizations, were developed to abate myriad issues, including inclement weather, social isolation and feelings of loneliness, replacements for in-person services, and lack of public transportation.

We tried on different occasions to use Zoom and Google Meets to bring folks together, so they have some human contact with somebody else other than themselves.
Some of them, if they just can’t find a sitter for the kids, we would say, hey, weather permitting, we’ll come out to your car… we are just trying really hard to be accommodating.
Pretty much all clients now are either texting or calling me on my cell phone. I have to be careful because clients now call me… for example, five o’clock on a Saturday.
Telehealth… we were just having a conversation this morning about the issues that we’re having with that because we’re finding that throughout the entire company, only 5% of patients are actually doing the actual face or the visual communication.
When necessary, we arrange for folks to have an Uber for them to, you know, get to their medical appointments.
We’ve had to get creative with screening ahead of time on the phone. And then, of course, checking their temperature and asking them questions before [clients] come in the door.
We would send a consent via email. We have to actually send out a consent asking if you want to continue with our program. We would send them copies of their consents, and they would just respond back like yes or no, and then we would proceed accordingly.

Key recommendations to abate disruptions

Respondents’ recommendations to address future disruptions and disparities followed a common thread of responses centered around the issue of communication. For example, participants contended that health departments were not clear on which services were being offered or the format for those services being provided, whether it be virtually or in person. Most organizations continued to provide HIV testing and other services; however, communication that such services were available during the pandemic was lacking. Participants noted that communication regarding services, such as mental health, specifically directed to LGBTQ + and people of color was not clear. Hence, the main recommendation offered by participants is to overhaul all means of communication between funding agencies (e.g., Centers for Disease Control and Prevention, state and local health departments) and HIV stakeholders, especially community agencies offering HIV services across the state.

Some [places], although they did offer HIV testing previously… now, this is complicated because on their website they provide the information that they do. But when you actually call them, they say that they actually don’t do it.
HIV prevention side in the state. Sometimes, communication just could have been better. I mean, especially within our health department… especially working from home and not in the building, communication could have been better about what was going on.
I felt like the health department was offering testing, but they didn’t…there wasn’t any messaging. Like there could have been some messaging on the radio; every slot was cheap. There could have been some billboards or could have been some type of mass communication telling people where they could go and get tested.
Just educating what resources and services are still available, you know, during the shutdown. And then, how to access things that clients possibly need like mental health resources because mental health is a big thing right now… just making sure that resources are reliable and inclusive, specifically for LGBTQ and people of color.

Minoritized groups disproportionately affected

As participants described structural issues that pre-dated the pandemic, and the disruptions to services, they also highlighted minoritized groups disproportionately affected by the pandemic. In light of the main recommendation, i.e., better communication, made by participants, it is important to emphasize these populations as they might need targeted forms of communication in case of future emergencies.

A lot of the people that were working were not here legally. They were undocumented, and they were very nervous to talk to us. So, we had to give them that reassurance that [they could still receive services].
Especially in my community, to get people if there’s ever a vaccine, Black people are going to be the last people to take it.
It was; it still does continue to be a bit of an issue… because of living situations amongst Arabic and Hispanic populations. [COVID] is spreading quite quickly because there’s just so many people living in one residence.
Now, the Amish population that’s a little different. They, once they figured out that the health department was going to call them, they just completely stopped getting tested. So, they’re really only getting tested if they have an employer that’s making them.

The literature suggests that COVID brought to light previous fragile structural conditions of healthcare [ 31 ], such as those identified by this study’s participants. The HIV field, from research to community action, has a rich history of adapting to political and social challenges since the beginning of the global and U.S. epidemic in the 1980s. Organizations and providers offering HIV services have been creative in addressing HIV stigma, limited funding streams, and political challenges. Nonetheless, when the World Health Organization (WHO) declared Sars-CoV-2 as the global “COVID-19 pandemic” in 2020, these same organizations and their service providers continued to help their clients again in the face of structural issues and political inaction [ 32 ].

The data from this study come from diverse HIV services stakeholders representing several regions across Michigan. MHACs format and processes engender involvement and accountability [ 24 , 25 , 26 ], challenged by personal and professional disruptions, many of which pre-dated the epidemic, particularly among MHAC members living with HIV. Having found a high degree of cohesiveness among study participants indicates that the qualitative data we collected reflect the opinions/sensibilities of the Council as a body that oversees HIV service provisions in Michigan. While the pandemic disrupted all HIV services (e.g., HIV testing, PrEP education, referrals to primary care, among others), the participants identified issues pre-dating the pandemic, such as poverty, housing insecurity, lack of transportation, and others. The extant literature helps to explain this study’s participants’ preoccupations with specific populations as it is known that, for the duration of the pandemic, politics enabled governments to put at risk various vulnerable groups—Black, indigenous, people of color, refugees, asylum seekers, and immigrants. Furthermore, our findings show that the effects of the COVID-19 pandemic on the disruption of HIV services were experienced differently and uniquely by each group. This indicates the need for a culturally-informed approach to recommendations like increased communication and guidelines in future emergencies.

The early months of the pandemic in 2020 were marked by shutdowns and shelter-in-place orders across the country, and then more relaxed regulations that differed across the country. By following state and local mandates, organizations offering HIV services differed in how quickly and how thoroughly they could keep their doors open and/or provide services in creative ways. Across Michigan, curbside services were widely used so that clients could safely remain in their vehicles. Like other locales, Michigan providers offered counseling, services, and support services via telephone and/or video conferencing as they developed creative ways to keep up with paperwork using email and other virtual means.

Our data show that the pandemic has been a long period of disruptions, setbacks, and triumphs. For those who did not have a car, the cold weather in Michigan posed a barrier to providing outside services during the extended winter months. Having been longer than several other states, Michigan’s stay-at-home order began on March 24, 2020, and ended on June 5, 2020. Governor Gretchen Whitmer and Health Department Director Elizabeth Hertel began to move away from initial mandates in early 2021 and encouraged people, along with service providers, to get vaccinated. Governor Whitmer vetoed legislation attempting to prevent her administration from using the public threat alert system to send out notifications regarding new mask rules. Michigan ended all restrictions on masking and gathering requirements towards the end of June 2021 [ 33 ].

This study is limited in that not all MHAC members were able to provide interviews. Although the majority of the Council participated, there might be areas of the state that were not fully represented in the sample. We also did not focus on how the pandemic affected services specifically to groups of individuals with different types and degrees of vulnerabilities– e.g., MSM, transgender people, and others. However, our research conducted through the Michigan HIV/AIDS Council is the first of its kind. Many states are required to have similar planning bodies to bring the community and lived perspectives at the state level to plan and execute the ending of HIV. Our approach to collecting local responses to the COVID-19 pandemic disruptions through interviews with MHAC members provides novel suggestions to how local responses can translate to state and national outcomes to said disruptions around HIV, especially communications. Furthermore, our data serve as a guide to historically document local responses to the COVID-19 pandemic by HIV service providers. This will catalog disruption responses in an expedited manner to propel research and innovation in light of new pandemics and world emergencies. Our study is not without impact of bias as researchers’ bias and participants’ social desirability bias are often present in qualitative research.

Implications and recommendations

As we hoped to understand the impact of COVID-19 on HIV services, we sought information from collaborative governance comprised of multiple stakeholders [ 22 ] to develop a statewide plan for HIV prevention and care [ 23 ]. This study’s participants suggested that better communication from the Michigan Department of Health and Human Services, particularly its HIV units, might have been helpful to those providers offering HIV services. Confusion about shelter-in-place and shut down orders and HIV service discontinuity across the state were key issues identified by participants. Therefore, their recommendation is to overhaul all means of communication between funding agencies (e.g., Centers for Disease Control and Prevention, state and local health departments) and HIV stakeholders, especially community agencies offering HIV services across the state. In a personal communication with Dawn Lukomski, Section Manager, Division of HIV and STI Programs (DHSP), she explained that the Michigan Department of Health and Human Services communicated broad information to the medical providers via press releases, press conferences, and the department’s website [ 27 ]. The Division of HIV/STI Programs communicated to HIV Prevention and Care agencies via webinars, monthly check-ins with funded agencies, our website ( www.michigan.gov/hivsti ), newsletters, and email (Personal Communication).

Our findings reflect a burgeoning literature showing that COVID-19 diminished community-based organizations’ ability to sustain the continuity of HIV services, sometimes making it uncertain that HIV infections in the U.S. will decrease by 90% within the current decade. Respondents contended that communication that clarifies specific orders and procedures that administrators and providers should follow in emergencies like the pandemic might abate the disruptions that threaten the continuity of HIV services at the dawn of a pandemic, now and in the future.

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Fauci AS, Redfield RR, Sigounas G, Weahkee MD, Giroir BP. Ending the HIV Epidemic. JAMA. 2019;321(9):844. http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2019.1343 .

Zhang SX, Wang Y, Rauch A, Wei F. Unprecedented disruption of lives and work: Health, distress and life satisfaction of working adults in China one month into the COVID-19 outbreak. Psychiatry Res. 2020;288:112958. https://linkinghub.elsevier.com/retrieve/pii/S0165178120306521 .

Bouey JZH, Han J, Liu Y, Vuckovic M, Zhu K, Zhou K et al. A case study of HIV / AIDS services from community-based organizations during COVID-19 lockdown in China. 2023;1–11.

Pirtle W, Wright T. Structural gendered racism revealed in pandemic times: Intersectional approaches to understanding race and gender health inequities in COVID-19. Gend Soc. 2021;35(2):168–79.

Article   Google Scholar  

Simmons A, Chappel A, Kolbe AR, Bush L, Sommers BD. Health disparities by Race and Ethnicity during the COVID-19 pandemic: current evidence and policy approaches. Washington, DC: Office of the Assistant Secretary for Planning and Evaluation, U.S. Department of Health and Human Services.; 2021.

Google Scholar  

Kay ES, Musgrove K, From. HIV to Coronavirus: AIDS service organizations adaptative responses to COVID-19, Birmingham, Alabama. AIDS Behav. 2020;24(9):2461–2. https://doi.org/10.1007/s10461-020-02879-1 .

Strathdee SA, Martin NK, Pitpitan EV, Stockman JK, Smith DM. What the HIV pandemic experience can teach the United States about the COVID-19 response. JAIDS J Acquir Immune Defic Syndr. 2021;86(1):1–10. https://journals.lww.com/ https://doi.org/10.1097/QAI.0000000000002520 .

Bartik AW, Bertrand M, Cullen Z, Glaeser EL, Luca M, Stanton C. The impact of COVID-19 on small business outcomes and expectations. Proc Natl Acad Sci. 2020;117(30):17656–66. https://doi.org/10.1073/pnas.2006991117 .

Palinkas LA, Springgate BF, Sugarman OK, Hancock J, Wennerstrom A, Haywood C, et al. A rapid assessment of disaster preparedness needs and resources during the COVID-19 pandemic. Int J Environ Res Public Health. 2021;18(2):1–21.

Brown S. 5 ways COVID-19 affects community-based organizations. DTC Perspect. 2020.

Stephenson R, Chavanduka TMD, Rosso MT, Sullivan SP, Pitter RA, Hunter AS et al. Sex in the time of COVID-19: Results of an online survey of gay, bisexual and other men Who have sex with men’s experience of sex and HIV prevention during the US COVID-19 Epidemic. AIDS Behav. 2021;25(1):40–8. https://doi.org/10.1007/s10461-020-03024-8 .

Dunlop A, Lokuge B, Masters D, Sequeira M, Saul P, Dunlop G et al. Challenges in maintaining treatment services for people who use drugs during the COVID-19 pandemic. Harm Reduct J. 2020;17(1):26. https://harmreductionjournal.biomedcentral.com/articles/ https://doi.org/10.1186/s12954-020-00370-7 .

Restar AJ, Garrison-Desany HM, Adamson T, Childress C, Millett G, Jarrett BA, et al. HIV treatment engagement in the context of COVID-19: an observational global sample of transgender and nonbinary people living with HIV. BMC Public Health. 2021;21(1):1–11.

Kantamneni N. The impact of the COVID-19 pandemic on marginalized populations in the United States: A research agenda. J Vocat Behav. 2020;119:103439. https://linkinghub.elsevier.com/retrieve/pii/S0001879120300646 .

Sanchez TH, Zlotorzynska M, Rai M, Baral SD. Characterizing the impact of COVID-19 on men Who have sex with men across the United States in April, 2020. AIDS Behav. 2020;24(7):2024–32. https://doi.org/10.1007/s10461-020-02894-2 .

Santos G-M, Ackerman B, Rao A, Wallach S, Ayala G, Lamontage E, Economic et al. Mental health, HIV prevention and HIV treatment impacts of COVID-19 and the COVID-19 response on a global sample of cisgender gay men and other men Who have sex with men. AIDS Behav. 2021;25(2):311–21. https://link.springer.com/ https://doi.org/10.1007/s10461-020-02969-0 .

Qiao S, Li Z, Weissman S, Li X, Olatosi B, Davis C et al. Disparity in HIV service interruption in the outbreak of COVID-19 in South Carolina. AIDS Behav. 2021;25(1):49–57. https://link.springer.com/ https://doi.org/10.1007/s10461-020-03013-x .

Mistler CB, Curley CM, Rosen AO, El-Krab R, Wickersham JA, Copenhaver MM et al. The impact of COVID-19 on access to HIV prevention services among opioid-dependent individuals. J Community Health. 2021;(0123456789). https://doi.org/10.1007/s10900-021-00979-0 .

Ostrach B, Buer LM, Armbruster S, Brown H, Yochym G, Zaller N. COVID-19 and rural harm reduction challenges in the US Southern Mountains. J Rural Heal. 2021;37(1):252–5.

MacCarthy S, Izenberg M, Barreras JL, Brooks RA, Gonzalez A, Linnemayr S. Rapid mixed-methods assessment of COVID-19 impact on latinx sexual minority men and latinx transgender women. PLoS One. 2020;15(12 December):1–15. https://doi.org/10.1371/journal.pone.0244421 .

Pinto RM, Park S. COVID-19 pandemic disrupts HIV continuum of care and prevention: Implications for research and practice concerning community-based organizations and frontline providers. AIDS Behav. 2020;24(9):2486–9. https://link.springer.com/ https://doi.org/10.1007/s10461-020-02893-3 .

Ansell C, Gash A. Collaborative governance in theory and practice. J Public Adm Res Theory. 2007;18(4):543–71. https://academic.oup.com/jpart/article-lookup/doi/ https://doi.org/10.1093/jopart/mum032 .

Michigan HIVAIDS, Council. Mission of the MHAC. 2022. https://www.michigan.gov/mdhhs/keep-mi-healthy/chronicdiseases/hivsti/michigan-hiv-aids-council .

Emerson K, Nabatchi T. Collaborative governance regimes. Georgetown University Press; 2015.

Provan KG, Milward HB. A preliminary theory of interorganizational network effectiveness: a comparative study of four community mental health systems. Adm Sci Q. 1995;40(1):1. https://www.jstor.org/stable/2393698?origin=crossref .

Scott TA, Thomas CW, When do public managers choose collaborative governance. unpacking the collaborative toolbox: Why and strategies? Policy Stud J. 2017;45(1):191–214. https://onlinelibrary.wiley.com/doi/ https://doi.org/10.1111/psj.12162 .

Michigan Department of Health and Human Services. HIV & STIs in Michigan. 2022. https://www.michigan.gov/mdhhs/keep-mi-healthy/chronicdiseases/hivsti .

Dobbins GH, Zaccaro S, The effects of group cohesion and leader behavior on subordinate satisfaction. Group & organization managemen. Gr Organ Manag. 1986;11(3):203–19. https://doi.org/10.1177/105960118601100305 .

Padgett D. Qualitative methods in social work research. 2nd ed. SAGE; 2008.

Coreil J. Group interview methods in community health research. Med Anthropol. 1994;16(1–4):193–210. http://www.tandfonline.com/doi/abs/ https://doi.org/10.1080/01459740.1994.9966115 .

Daher-Nashif S. In sickness and in health: The politics of public health and their implications during the COVID‐19 pandemic. Sociol Compass. 2022;16(1). https://onlinelibrary.wiley.com/doi/ https://doi.org/10.1111/soc4.12949 .

World Health Organization. Coronavirus disease 2019. WHO. 2020 [cited 2020 Apr 10]. https://www.who.int/europe/emergencies/situations/covid-19 .

Boucher D. Michigan drops recommendation for masks in schools, other indoor settings. Detroit Free Press; 2022.

Download references

Acknowledgements

We wish to thank Leon Golson for his help us get access to research participants and his valuable input in all phases of this project.

Internal Pilot Funding from the University of Michigan School of Social Work.

Evan Hall were funded by Student Opportunities for AIDS/HIV Research (SOAR) Program, National Institute of Mental Health and the Office of Behavioral and Social Science Research, (1R25MH126703-01), University of Michigan, Ann Arbor.

Carol Lee was funded by a National Institute on Alcohol Abuse and Alcoholism (NIAAA) T-32 (T32AA007477) Postdoctoral Research Training Fellowship at the Addiction Center at the University of Michigan.

Author information

Authors and affiliations.

School of Social Work, University of Michigan, 1080 South University Avenue, Ann Arbor, MI, USA

Rogério M. Pinto, Evan Hall, Vitalis Im & Sunggeun (Ethan) Park

Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA

Carol A. Lee

You can also search for this author in PubMed   Google Scholar

Contributions

Pinto, Principal Research Investigator, conceptualized the study, established research question, data analysis, and wrote final draft of the manuscript; Hall wrote background to manuscript, and coded interviews; Im coded of interviews and assembled methods section; Lee coded interviews, reviewed manuscript, supervised interviews; Park help to conceptualized paper, project formation, and reviewed final manuscript.

Corresponding author

Correspondence to Rogério M. Pinto .

Ethics declarations

Ethics approval and consent to participate.

This research involved human participants, and it was therefore performed in accordance with the Declaration of Helsinki. Approval for this study was waived by the Research and Ethics Compliance Committee at the University of Michigan decided that no IRB approval was needed [HUM00183927– Ame00111901]. The study was exempt because we used only collection of information by surveys and interviews with adult participants who are members of a public council, Michigan HIV/AIDS Council, and the materials were used for improving council procedures and educational purposes only. Informed consent was obtained for all participants prior to any interview.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Rights and permissions.

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ . The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Cite this article.

Pinto, R.M., Hall, E., Im, V. et al. Disruptions to HIV services due to the COVID pandemic in the USA: a state-level stakeholder perspective. BMC Health Serv Res 24 , 196 (2024). https://doi.org/10.1186/s12913-024-10609-9

Download citation

Received : 01 April 2023

Accepted : 17 January 2024

Published : 13 February 2024

DOI : https://doi.org/10.1186/s12913-024-10609-9

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

  • HIV prevention
  • HIV services
  • COVID disruptions
  • Responses to COVID-19

BMC Health Services Research

ISSN: 1472-6963

research paper on hiv/aids

Click through the PLOS taxonomy to find articles in your field.

For more information about PLOS Subject Areas, click here .

Loading metrics

Open Access

Peer-reviewed

Research Article

The emergence and evolution of the research fronts in HIV/AIDS research

* E-mail: [email protected] (DF-O); [email protected] (VMC)

Affiliation Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico

ORCID logo

Affiliation Institute of Data Science, Maastricht University, Maastricht, The Netherlands

Affiliation Instituto de Biología, Universidad Nacional Autónoma de México, Mexico City, Mexico

Affiliation Colegio de la Frontera Sur, Chiapas, Mexico

Affiliation Centro de Física Aplicada y Tecnología Avanzada, Universidad Nacional Autónoma de México, Queretaro, Mexico

  • David Fajardo-Ortiz, 
  • Malaquias Lopez-Cervantes, 
  • Luis Duran, 
  • Michel Dumontier, 
  • Miguel Lara, 
  • Hector Ochoa, 
  • Victor M. Castano

PLOS

  • Published: May 25, 2017
  • https://doi.org/10.1371/journal.pone.0178293
  • Reader Comments

Fig 1

In this paper, we have identified and analyzed the emergence, structure and dynamics of the paradigmatic research fronts that established the fundamentals of the biomedical knowledge on HIV/AIDS. A search of papers with the identifiers "HIV/AIDS", "Human Immunodeficiency Virus", “HIV-1” and "Acquired Immunodeficiency Syndrome" in the Web of Science (Thomson Reuters), was carried out. A citation network of those papers was constructed. Then, a sub-network of the papers with the highest number of inter-citations (with a minimal in-degree of 28) was selected to perform a combination of network clustering and text mining to identify the paradigmatic research fronts and analyze their dynamics. Thirteen research fronts were identified in this sub-network. The biggest and oldest front is related to the clinical knowledge on the disease in the patient. Nine of the fronts are related to the study of specific molecular structures and mechanisms and two of these fronts are related to the development of drugs. The rest of the fronts are related to the study of the disease at the cellular level. Interestingly, the emergence of these fronts occurred in successive "waves" over the time which suggest a transition in the paradigmatic focus. The emergence and evolution of the biomedical fronts in HIV/AIDS research is explained not just by the partition of the problem in elements and interactions leading to increasingly specialized communities, but also by changes in the technological context of this health problem and the dramatic changes in the epidemiological reality of HIV/AIDS that occurred between 1993 and 1995.

Citation: Fajardo-Ortiz D, Lopez-Cervantes M, Duran L, Dumontier M, Lara M, Ochoa H, et al. (2017) The emergence and evolution of the research fronts in HIV/AIDS research. PLoS ONE 12(5): e0178293. https://doi.org/10.1371/journal.pone.0178293

Editor: Dimitrios Paraskevis, National and Kapodistrian University of Athens, GREECE

Received: November 16, 2016; Accepted: May 10, 2017; Published: May 25, 2017

Copyright: © 2017 Fajardo-Ortiz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper and its Supporting Information files.

Funding: The authors received no specific funding for this work.

Competing interests: The authors have declared that no competing interests exist.

Introduction

The Human Immunodeficiency Virus/ Acquired Immunodeficiency Syndrome (HIV/AIDS) is a global health problem: over 70 million people have been infected with HIV, 35 million have died and 36.7 million people currently live with the disease [ 1 ]. HIV/AIDS is one of the most studied infection diseases with more than 260,000 papers (mentioning the topic) listed in GOPubMed [ 2 ] and more than 42,000 papers (mentioning HIV/AIDS in the title) in the Web of Science [ 3 ] spanning over thirty year of scientific research. HIV/AIDS is studied by a plurality of biomedical disciplines like epidemiology [ 4 ], virology [ 5 ], immunology [ 6 ] or drug development [ 7 ] and non-biomedical disciplines like social sciences [ 8 ] and humanities [ 9 ]. All the biomedical disciplines working on HIV/AIDS strongly rely on a solid scientific consensus, which explains the clinical manifestation of HIV/AIDS in terms of the virus interactions with the immune system cells; the behavior and demography of the immune system cells, and, most importantly, the virus interaction with the biomolecular machinery of the host cells [ 10 – 12 ]. Two features are believed to be at the core of the scientific consensus on HIV/AIDS: the natural history of the HIV infection (the number of CD4+ cells and HIV RNA copies plotted over the time) [ 11 ] and the virus replication cycle (from the virus entry to the virus assembly, budding and maturation) [ 10 , 12 ].

Paradigms are the keystone of research communities [ 13 , 14 ], for they provide a foundation for members of the community; they also define the questions, the standards, the rules and the expected results that drive research efforts [ 13 , 14 ]. Paradigms of HIV/AIDS research are often presented in a timeline format [ 12 , 15 ]. However, while such a historical perspective is informative, they present two disadvantages: the first is that the selection of the most relevant discoveries is arbitrary, i.e., not supported by scientometric evidence, while the second disadvantage is that the paradigms are not presented as the key elements of the organizing process of the research communities.

The study of the emerging research fronts offers the possibility of analyzing the relationship between the paradigms and the organizational process of the scientific communities [ 14 , 16 , 17 ]. Research fronts can be considered as modules or clusters in a citation network of papers, i.e., sparse sub-networks of papers that exhibit dense connections [ 18 ].

It must be pointed out that research fronts are the footprint of the scientific communities. That is, citation patterns of scientists exhibit homophily [ 14 , 19 ], which is caused by the scientists trend to cite those papers that focus in similar topics with a similar approach -and very often they cite those papers that strengthen the papers argumentation [ 14 , 19 , 20 ]. Citations tend to point toward those discoveries that the research (sub)communities consider the most relevant ones. i.e., the paradigms [ 13 , 14 , 21 – 23 ]. Therefore, paradigms occupy the most central location in the citation networks; they are the seeds that organize the emergence of the research fronts [ 14 , 17 ]. To explain the emergence of the biomedical consensus on HIV/AIDS requires a study of the structure and dynamics of the research fronts.

Previous studies using the research fronts analysis approach were mainly focused in topics from engineering [ 24 , 25 ], biotechnologies [ 18 ] and scientometrics [ 26 ]. There are some studies that focused in the structure of the biomedical knowledge on specific diseases [ 14 , 16 , 17 , 27 , 28 ]. Our previous research has been particularly focused in the core region of the literature networks [ 14 , 17 , 27 ]. By doing this we have discovered the key feature of the organization of the knowledge on cervical cancer [ 27 ] and Ebola fever [ 17 ]. Others have reported the evolution of research fronts in anthrax research [ 16 ], cancer research [ 28 ] and cardiovascular medicine [ 28 ]. By analyzing the structure and evolution of HIV/AIDS knowledge we further our understanding of the nature of the biomedical knowledge discovery.

Through a combination of text mining and network analysis, we sought to understand the emergence and evolution of the research fronts (the footprints of the research communities) that produced the paradigmatic explanation of this disease.

Methodology

  • A search of papers on HIV/AIDS was performed in the Web of Science [ 3 ] during March, 2017. The search criteria were the following: TITLE: ("HIV AIDS") OR TITLE: ("Human immunodeficiency virus") OR TITLE: ("acquired immune deficiency syndrome") OR TITLE: (hiv-1). Refined by: DOCUMENT TYPES: (ARTICLE). Timespan: All years. Indexes: SCI-EXPANDED, SSCI, A&HCI, CPCI-S, CPCI-SSH, BKCI-S, BKCI-SSH, ESCI. 60,464 papers were found.
  • A network model was built with the papers found in the Web of Science by using the software HistCite [ 29 ]. Then, the network model was analyzed and visualized with Cytoscape [ 30 ]. The indegree distribution of the network was evaluated to determine if it fitted to a power law function (y = ax^b).
  • A core sub-network of papers with an indegree ≥ 28 was then closely examined. Normally, the indegree distribution in citation networks follows a power law function such that only a few papers are very well cited, while most papers are not [ 31 ]. This applies to the case of HIV/AIDS research as we report. We selected the papers with an indegree ≥ 28 because they are a small and workable quantity of papers that account for nearly half of the communication process through the citations network as it is reported in the results section (The selected papers received 42,8911 out of 679,497 citations from the HIV/AIDS literature). Top cited papers appear related to the paradigmatic milestones of a particular research topic.
  • A cluster analysis based in the Newman modularity [ 32 ] was performed on the core sub-network using Clust&see, a Cystoscape plug-in [ 33 ]. This analysis divided the sub-network of citation in several research fronts (clusters or modules of papers). This clusters are defined by Newman as “groups of vertices within which connections are dense but between which they are sparse” [ 32 ].
  • The sub-network was displayed by using the “yFiles organic” algorithm, which is based on the force-directed layout [ 30 ]. This algorithm considers the nodes as charged particles that exhibit repulsive forces and the vertices as springs. In this layout, the papers that cite the same papers tend to stick together making easier the visualization of the research fronts.
  • The number of papers of each research front was plotted over the years in order to track the dynamics of the research fronts.
  • The content of the identified research fronts -the abstract of their papers- was analyzed with KH Coder [ 34 ], a software for quantitative content analysis (Text mining). KH Coder delivered several outputs. However, we considered that the most informative output was the list of the most distinctive words which provided key information about what was the main focus of the papers of each front. Additionally, the five papers with the highest indegree within each of the research fronts were identified. in order to provide a context to the reading of the text mining results.
  • Because front 1 “patient” is the largest and most central front according to our results, a cluster analysis was then performed on it by using Clust&see. The sub-modules that form front 1 were identified.

The network model

60,464 published articles on HIV/AIDS were identified by keyword search over the Thomson Reuters Web of Science. 57,485 of these papers form a single network of 679,497 inter-citations. The structural network analysis performed by Cytoscape showed that the distribution of the indegree in this network fitted a power law function (y = ax^b, a = 51,954, b = -1.79, correlation = 0.827, R-squared = 0.909). This means that a very small number of papers receive the overwhelming majority of citations while most papers receive few if any citations [ 31 , 35 ].

We selected papers with an indegree ≥ 28, that is, 5,933 documents. Together, these papers receive 63% of the inter-citations that form the whole network (42,8911 of 679,497), and would represent a relevant part of the historical core of the HIV/AIDS research as it was explained in the methodology section. These 5,933 highly cited papers formed a network of 86,963 inter-citations ( Fig 1 ). The cluster network analysis identified fourteen clusters (or modules as defined by Newman). However, one cluster were too small to be considered relevant research fronts. The thirteen clusters were formed by 12,303, 9,115, 7,407, 6,746, 5,680, 4,763, 4,696, 3507, 2,861, 2,768, 2,597, 2,053, and 1,662 inter-citations.

thumbnail

  • PPT PowerPoint slide
  • PNG larger image
  • TIFF original image

The model is displayed by using the “yFiles organic” algorithm. The color of nodes (representing the papers) and vertices indicates which research front they belong to.

https://doi.org/10.1371/journal.pone.0178293.g001

The organization and dynamics of the research fronts

The main interaction among the seven research fronts is shown in Fig 2 . In this figure, each of the research fronts is represented by a single node, and the edges represent the sum of the inter-citations among the fronts ( Fig 2 ). Therefore, this graphical synthesis allows us to understand how the paradigmatic core of HIV/AIDS research was organized. However, the complete panorama can be only understood when Fig 2 is simultaneously read with Fig 3 and with Table 1 and S1 Table . Fig 3 shows the dynamics of the research fronts by plotting the number of citation papers per year of each research. In Fig 3 , the fronts are shown in different plots according to the period of time in which the fronts reached their maximum number of papers per year: between 1990 and 1991 ( Fig 3A ), between 1996 and 1999 ( Fig 3B ), and between 2004 and 2007 ( Fig 3C ). S1 Table provides the detailed description of each research front, including its structural features; the main topics of each research fronts according to the text mining analysis, and the list of the papers with the highest indegree within each research front. Table 1 groups the fronts according to the organization level (Individual, cellular-tissular and molecular) and the period in which the number of papers of each front peaked. The figures and the tables together offer an interesting view of the evolution and organization of HIV/AIDS research in the three first decades:

thumbnail

Each node represents one of the seven research fronts. The edges represent the sum of the inter-citations between two clusters. Only the interactions formed by a minimal of 500 inter-citations or the largest interaction (If the front have none interaction ≥ 500 inter-citations) of each front are shown.

https://doi.org/10.1371/journal.pone.0178293.g002

thumbnail

A: Research fronts whose number of papers peaked between 1990 and 1991, B: peaked between 1996 and 1999 and C: peaked between 2004 and 2007.

https://doi.org/10.1371/journal.pone.0178293.g003

thumbnail

https://doi.org/10.1371/journal.pone.0178293.t001

HIV/AIDS research is reductionistly-organized, following a hierarchy of biological structures and systems ( Fig 2 , Table 1 ). That is, at the core of the network is located the front 1 “patient” (Figs 1 and 2 ) which focus on the study of the HIV/AIDS phenomenon at individual-systemic level. Surrounding front 1, there are research fronts (Front 3 “isolate,” front 9 “Cytotoxic T lymphocyte” and front 10 “brain” in Fgs 1 and 2) that are related to the study of specific events of the disease at cellular level ( Table 1 and S1 Table ). In the most external part of the network model there are most of the fronts related to the study of molecular structures and mechanisms (Front 5 “reverse transcriptase inhibitor” front 6 “assembly,” front 7 “protease inhibitor” front 8 “integration,” front 11 “replication,” front 12 “nucleocapsid” front and 13 “infectivity”; see Figs 1 and 2 and Table 1 and S1 Table ). On the other hand, Front 2 “glycoprotein 120” and front 5 “reverse transcriptase inhibitor” are strongly connected to front 1 “patient” (Figs 1 and 2 ) However, the research in these fronts (2 and 5) is oriented to the development of treatments (immuno-therapies and small molecules drugs, respectively), which may explain their strong connection to front 1. Notice that fronts 3 and 2 function as transition zones in HIV/AIDS research connecting the different levels of observation (systemic, tissular-to-cellular and molecular) (Figs 1 and 2 ).

On the other hand, the research fronts clearly can be grouped in three different periods of time in which the fronts reach their maximum number of papers per year: 1990–1991, 1996–1999 and 2004–2007 ( Fig 3 ). In order to properly read Fig 3 it is important to keep in mind the dramatic changes in the epidemiology of HIV/AIDS in the United States (USA) that happened between 1993 and 1995 [ 36 ]. In that period, the number of AIDS diagnosis and deaths reached their maximum and then declined[ 36 ]. Simultaneously, in 1995, the number of persons living with HIV began to rise[ 36 ]. Therefore, we can consider the existence of two stages in the history of HIV/AIDS: before 1995 in which AIDS was the main concern and after 1995 when HIV infection is at the center of HIV/AIDS research. A second important consideration to understand Fig 3 is that the phase of expansion or growth in science (the “normal” science of Thomas Kuhn) follows the publication of those scientific achievements that organize the subsequent research[ 13 ]. This would explain that the peaks in Fig 3 generally occurred years after the publication of the papers with the highest degree ( Fig 3 and S1 Table ). The peaks in figure can be considered a delayed response to fundamental events and discoveries in the history of HIV/AIDS research. A third consideration is that the network model is made from the ten percent of papers with the highest indegree. Therefore, the succession of research fronts observed in Fig 3 does not mean the end of the research on specific topics but that these topics are not longer in the core of HIV/AIDS research.

Fronts 2 “glycoprotein 120,” 4 “tat-tar,” 5 “reverse transcriptase inhibitor” and 10 “brain” emerged immediately after front 1 and peaked in the 1990 and 1991 years. The expansion of these fronts in this early stage in the history of HIV/AIDS research suggests that these fronts are relevant to the description, explanation or intervention of AIDS. For example, it has been pointed out that tat (Trans-activator of transcription) protein, which is essential for virus replication, could be involved in the progression to AIDS and in the development of Kaposi's sarcoma lesions.[ 37 , 38 ] Along the same line, the interaction between glycoprotein 120 and CD4 is the first event in the replication cycle and is considered fundamental to virus entry.[ 39 ] It is important to keep in mind that the depletion of lymphocytes expressing CD4 is considered the most severe hematological feature of AIDS.[ 39 ] Similarly, encephalopathy is one of the most dominant feature of AIDS.[ 40 ] Finally, a reverse transcriptase inhibitor, zidovudine (AZT) was the first drug approved by the United States Food and Drug Administration (FDA) to treat AIDS.[ 41 ]

Research fronts 1 “patient,”and 3 “isolate,” reached their maximum number of papers per year between 1996 and 1999 ( Fig 3 ). The peaks of these fronts follow the changes in the epidemiology of HIV/AIDS in the USA. Therefore, these fronts are possibly related to a collective response from the scientific community to the new reality of the disease. The research in front 1 is the largest, central and most clinical among the fronts (Figs 1 and 2 , and S1 Table ). This front connects the clinical and epidemiological manifestations of HIV/AIDS with their explanation at a cellular level. Because of the size, the centrality and clinical relevance, we decided to perform a second round of cluster analysis to identify the sub-modules that may conform front 1. We plotted the contribution of each sub-module to the evolution of front 1 in Fig 4 . Sub-module 1A, 1D and 1E are the key components of the 1999's peak ( Fig 4 ). The papers with the highest indegree in sub-modules 1A, 1D and 1E are, respectively, “Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment,”[ 42 ] “Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection”[ 43 ] and “Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy”.[ 44 ] These papers report and explain fundamental changes in the clinical reality of HIV/AIDS produced by the implementation of anti-retroviral therapies. Front 3 “isolate,” to the study of HIV tropism, i.e., the differential capacity of the HIV strains to infect and replicates in different cell types ( Table 1 ). Importantly, the availability of screening tools that allowed the identification of asymptomatic individuals infected with HIV and the use of anti-retroviral therapies make extensively available the blood and tissue samples from the patients that were fundamental to the emergence of front 3.

thumbnail

https://doi.org/10.1371/journal.pone.0178293.g004

On the other hand, most of the research fronts specialized in the study of specific molecular mechanisms and structures (fronts 6 to 9 and fronts 11 to 13) peaked either in the 1996–1999 or 2004–2007 periods ( Fig 3 ). It is important to notice that all these fronts emerged at the end of the first decade of HIV/AIDS research. The difference between fronts peaking in the second and the third periods is that the former decline earlier. In order to understand the evolution of these fronts is important to keep in mind that the scientific specialization is a continuous process of solving problems that follows the establishment of a paradigm (HIV-1 as the etiological agent of HIV/AIDS).[ 13 ] In that sense, the decline of fronts 8, 11 and 12 ( Fig 3B ) may be so because the scientific problem is either essentially solved or the changes in the HIV/AIDS epidemiology made less relevant the topics related to these fronts.

According to the Cytoscape analysis, the network of HIV/AIDS papers displays a power law distribution of their citations, which has important methodological implications. The first implication is that a research front (a citation network module) could be formed by other research fronts, which in turn can be partioned into sub-modules [ 44 ]. The second implication is that the nodes (papers) with the highest indegree tend to be more “cosmopolitan” i.e., they have the lowest clustering coefficient values [ 44 ]. That is, they could belong simultaneously to several fronts or any of them. Therefore, there are not clearly defined frontiers dividing the research fronts. However, the standard in the scientometrics study of research fronts seems to be to use clustering methods that define frontiers between the modules [ 14 , 17 , 18 , 24 , 25 , 27 , 28 ], probably because this is make much more understandable the community structure in a literature network. Moreover, our analysis reveals the front that is most relevant to each paper. Finally, the most important implication is that in a hierarchical literature network the most the papers with the highest indegree are related with the paradigms that organize a research field or topic [ 14 ]. Top cited papers have been extensively used to identify the scientific achievements that establish the standards of research practice of a particular community [ 14 , 17 , 22 , 23 , 27 , 28 , 45 , 46 ]. There are no set guidelines on the proportion of top cited papers that should be selected. However, there is a trade off between selecting the most informative papers and maintaining diversity of the information [ 14 , 17 ]. In this work, we used a minimal indegree of 30 to select the top cited papers, and in turn obtaining a considerable percentage of the citations. The selected papers consist of only ten percent of the network but they effectively account for two thirds of the citations. The selected papers are a reasonable representation of the paradigmatic core of HIV/AIDS research.

Once the HIV was recognized as the etiological factor HIV/AIDS research entered in normal science mode that is characterized by a high productivity and for a specialization of the researchers. By specialization we refer to “concentrate exclusively upon the subtlest and most esoteric aspects of the natural phenomena that concern his group” [ 12 ]. Once the paradigms are established, researchers focus on the details, the smaller range problems and solutions that the current paradigm provide [ 13 ]. Our results suggest that the emergence of several of the specialized research fronts was caused by the partition of the general problem in interacting elements. That is, HIV/AIDS research could be understood to some extent as a particular instance of part-whole science in which paradigms determine the abstraction of the parts that are considered the most relevant to explain the whole phenomenon [ 47 , 48 ].

The general structure and evolution of the research fronts in HIV/AIDS research shares similarities to that of anthrax and Ebola. The evolution of anthrax investigation began with a preliminary on the immunology of the disease [ 16 ]. From this, four research fronts emerged: “anthrax gene sequencing”, “vaccine research”, secondary research on PA (protective antigen) and LF (lethal factor), and “making and purifiying toxin” [ 16 ]. Subsequently, the research front on PA and LF split in three fronts: “specific PA research”, PA mediated delivery of other substances” and specific “LF research” [ 16 ]. Similarly, the evolution of the fronts in Ebola research are marked by a front related to the report of the epidemiology and the clinical manifestation of the disease [ 17 ]. A second front provide an explanation of the disease at tissue-cellular level [ 17 ]. Then, research on Ebola split into four research fronts, each one specialized in one different virus protein [ 17 ]. There is also a front aimed to the development of vaccines and other immunotherapies [ 17 ]. Similarly, the emergence of the fronts in HIV/AIDS research started with a general research front that provided the pathology of the disease and subsequently split into specialized fronts focused on the study of specific molecular mechanism of the virus replication cycle. In all three cases, the specialization of the research led to the emergence of research fronts focused in the study of the parts that are thought to be key in explaining the diseases. A report on the emergence of the research fronts in cancer and cardiovascular diseases showed that the specialization process in these types of diseases is complex [ 28 ]. Jones et al. reported fronts specialized on microarrays, targeted therapies, clinical trials, epidemiology and molecular etiology in cancer research [ 28 ], while in cardiovascular diseases the fronts are organized around drug-eluting stents, anti-platelet agents, pacemakers, hypertension and atrial fibrillation [ 28 ]. The difference between these two groups of diseases is that HIV/AIDS, anthrax and Ebola are infectious diseases with a clearly identified etiological agent while cancer and cardiovascular diseases are both complex multifactorial diseases [ 49 ].

This is the first time that the complex organization (and the evolution) of HIV/AIDS research is reported. Our research provides fundamental knowledge concerning the emergence of the paradigmatic explanation for HIV/AIDS and therefore makes a contribution to the understanding of the nature of biomedical knowledge. In addition, our work suggests that the development of the paradigmatic knowledge on HIV/AIDS in terms of the emergence and evolution of the research fronts followed two different routes. First, the emergence of the specialized fronts (molecular mechanism and structures and cellular process) was caused by the division of the general problem in their key process, element and interactions, which is related to the concept of part-whole science. Second, the dynamics of the fronts, particularly the evolution of front 1 “patient” and 2 “isolate”, appears to represent an adaptive and collective response from the scientific community to changes in the epidemiological (the decline in the morbidity and mortality of AIDS in the USA) and technological (the availability of treatments and screening tools) context of this health problem.

Supporting information

S1 table. description of the research fronts..

Structural properties; top 10 distinctive worlds, and list of the five papers with the highest indegree within each of the research fronts.

https://doi.org/10.1371/journal.pone.0178293.s001

Author Contributions

  • Conceptualization: DF-O VMC.
  • Data curation: DF-O.
  • Formal analysis: DF-O.
  • Investigation: DF-O.
  • Methodology: DF-O.
  • Project administration: DF-O.
  • Resources: DF-O.
  • Supervision: DF-O VMC.
  • Validation: DF-O.
  • Visualization: DF-O.
  • Writing – original draft: DF-O VMC ML-C LD MD ML HO.
  • Writing – review & editing: DF-O MD.
  • 1. World Health Organization. Global health observatory (GHO) data. URL. http://www.who.int/gho/tb/en . 2015 May.
  • View Article
  • Google Scholar
  • PubMed/NCBI
  • 4. Wilson D. HIV epidemiology: A review of recent trends and lessons. The World Bank: Washington DC. 2006.
  • 13. Kuhn TS. The Structure of Scientific Revolutions. Enlarged International Encyclopedia of Unified Science.
  • 48. Valadez Blanco EO. La parte y el todo en la explicación científica del cáncer (Dissertation). UAM-Iztapalapa.
  • Open access
  • Published: 17 September 2020

HIV/AIDS research in Africa and the Middle East: participation and equity in North-South collaborations and relationships

  • Gregorio González-Alcaide   ORCID: orcid.org/0000-0003-3853-5222 1   na1 ,
  • Marouane Menchi-Elanzi 2   na1 ,
  • Edy Nacarapa 3 , 4 &
  • José-Manuel Ramos-Rincón 2 , 5  

Globalization and Health volume  16 , Article number:  83 ( 2020 ) Cite this article

9933 Accesses

17 Citations

3 Altmetric

Metrics details

HIV/AIDS has attracted considerable research attention since the 1980s. In the current context of globalization and the predominance of cooperative work, it is crucial to analyze the participation of the countries and regions where the infection is most prevalent. This study assesses the participation of African countries in publications on the topic, as well as the degree of equity or influence existing in North-South relations.

We identified all articles and reviews of HIV/AIDS indexed in the Web of Science Core Collection. We analyzed the scientific production, collaboration, and contributions from African and Middle Eastern countries to scientific activity in the region. The concept of leadership, measured through the participation as the first author of documents in collaboration was used to determine the equity in research produced through international collaboration.

A total of 68,808 documents published from 2010 to 2017 were analyzed. Researchers from North America and Europe participated in 82.14% of the global scientific production on HIV/AIDS, compared to just 21.61% from Africa and the Middle East. Furthermore, the publications that did come out of these regions was concentrated in a small number of countries, led by South Africa (41% of the documents). Other features associated with HIV/AIDS publications from Africa include the importance of international collaboration from the USA, the UK, and other European countries (75–93% of the documents) and the limited participation as first authors that is evident (30 to 36% of the documents). Finally, the publications to which African countries contributed had a notably different disciplinary orientation, with a predominance of research on public health, epidemiology, and drug therapy.

Conclusions

It is essential to foster more balance in research output, avoid the concentration of resources that reproduces the global North-South model on the African continent, and focus the research agenda on local priorities. To accomplish this, the global North should strengthen the transfer of research skills and seek equity in cooperative ties, favoring the empowerment of African countries. These efforts should be concentrated in countries with low scientific activity and high incidence and prevalence of the disease. It is also essential to foster intraregional collaborations between African countries.

HIV infection and its clinical manifestation, AIDS, are considered a pre-eminent challenge for global public health [ 1 ], affecting populations worldwide since the 1980s. Despite the progress made in prevention and treatment programs, the disease is still pandemic, with the African continent being the hardest hit [ 2 ]. An estimated 37.9 million people were living with HIV in 2018, of whom 20.6 million lived in Eastern and Southern Africa, 5 million in Western and Central Africa, and 240,000 in the Middle East and North Africa. The same year saw about 770,000 deaths from this disease and 1.7 million new infections, 61% of which occurred in sub-Saharan Africa. Over half of the new cases in Eastern and Southern Africa were concentrated in Mozambique, South Africa, and Tanzania, while 71% of new infections in Western and Central Africa were in Cameroon, the Côte d’Ivoire, and Nigeria. In the Middle East and North Africa, two-thirds of new cases were registered in Egypt, Iran and Sudan [ 3 ]. In response to this challenge, researchers worldwide have worked to produce evidence on HIV/AIDS across a wide range of biomedical disciplines, including epidemiology, virology, immunology, and pharmacology, as well as in non-biomedical fields such as social sciences and the humanities. This body of work has situated HIV/AIDS among the most studied infectious diseases today [ 4 ].

Bibliometrics is a method that enables the quantitative and qualitative assessment of scientific research in any area of knowledge, at an individual, institutional, or national level [ 5 ]. In that sense, ample literature has been published on bibliometric analyses of HIV/AIDS research since the 1980s [ 6 , 7 ], including some papers that focus specifically on the regions most affected by the virus and the infection, like Central Africa [ 8 ]; sub-Saharan Africa [ 9 ]; or on countries like Kenya, Uganda, Nigeria, or Lesotho [ 10 , 11 , 12 ]. However, many of these papers were published more than a decade ago and investigated the scientific production in the geographical areas analyzed. In the current context of globalization and predominance of cooperative work, Africans are under-represented in terms of authorship in collaborative research publications. This situation has led some investigators to call for studies that quantify authorship equity [ 13 ] and explore North-South relationships in research collaboration [ 8 ].

The overarching objective of the present study is to provide an up-to-date description of participation from Africa and the Middle East in the literature on HIV/AIDS published in high-visibility journals, and of the role played by researchers from African countries in publications produced in international collaboration. Our specific research questions were: (1) What was the contribution from Africa and the Middle East, both overall and by country, to the global scientific research output on HIV/AIDS? (2) Is North-South participation balanced international collaboration papers? and (3) Are there differences in the subject-area orientation between publications produced with or without participation from African and Middle Eastern authors on HIV/AIDS research?

The methodological process was as follows.

Identification of global scientific research production on HIV/AIDS

To identify the scientific literature on HIV/AIDs, we used the Medical Subject Headings (MeSH) thesaurus of the National Library of Medicine, selecting all of the descriptors related to HIV, human immunodeficiency related to HIV infection, and the development of vaccines for preventing or clinically treating the immunodeficiency. The final MeSH (plus their variants and synonyms) were: HIV, HIV Infections, Acquired Immunodeficiency Syndrome, and AIDS Vaccines.

Although the MeSH thesaurus is linked to the MEDLINE database, which is freely available through the PubMed platform, we performed a second search of the documents identified in MEDLINE and which were also indexed in the Web of Science Core Collection (WoS-CC) databases. Although this database does not cover all of the documents indexed in MEDLINE/PubMed, it does include all of the institutional affiliations (which MEDLINE started listing only in 2014), making it an ideal source for characterizing scientific production by country and the collaboration from Africa and the Middle East in HIV/AIDS publications during the study period.

The collection of journals in the WoS-CC, moreover, represents the information sources with the highest visibility at an international level. Thus, using that source to calculate our bibliometric study indicators allows a vision of the development of the most relevant and impactful research worldwide.

Definition of the document sample analyzed

Our literature search yielded 93,031 documents on HIV, 256,354 on HIV Infections, 76,359 on Acquired Immunodeficiency Syndrome, and 7528 on AIDS Vaccines. After removing duplicate descriptors, there were 298,718 unique documents. We then restricted the results to those published from 2010 to 2017 ( n  = 83,316) in order to focus the analysis on the most recent research. We ruled out the inclusion of documents from 2018 to avoid delays related to indexation, as at least a year is needed to ensure updated information related to the assignment of MeSH terms. We subsequently identified the documents that were also included in the WoS-CC databases by searching for all of the documents from the initial sample using their PMIDs (the PubMed identifier used as a reference in MEDLINE and included as a bibliographic field in WoS-CC). In total, 89.29% ( n  = 74,375) of the MEDLINE documents were also in the WoS-CC. This set of papers was further restricted to three document types: articles, reviews, and letters ( n  = 68,808), chosen because they are the most prominent papers for transmitting the results of original research (articles); situating and evaluating the development of research in a highly relevant way for other researchers (reviews); and contributing critical viewpoints, comments, relevant information, and perspectives on published studies (letters). The searches took place in November 2018. Figure  1 presents a flow chart showing the selection process for the sample of documents analyzed in the study.

figure 1

Flow chart for the selection of included documents

Download of bibliographic information and review of the standardization of data

Following the bibliographic search and document selection, we downloaded the bibliographic information from the selected records ( n  = 68,808), generating a relational database in Microsoft Access in order to enumerate and individualize the multiple entries contained in certain bibliographic fields. This is the case of institutional affiliations, as a single field collates the data for all co-authors’ institutions and countries. Likewise, the subject area field for the journal of publication may also have several assigned topics, and various MeSH and other text words are assigned to different documents to describe their content.

We also reviewed the standardization and quality of the data. For example, we looked at the years of publication, as the date of some documents’ public dissemination on the journal website differed from the definitive date of publication in the journal (the latter was taken as the reference). Likewise, we consolidated all the information on geographic origins from England, Scotland, Wales, and North Ireland—presented individually in the WoS-CC—under the UK.

Identification of participation from Africa and the Middle East in HIV/AIDS publications

To analyze the participation from Africa and the Middle East in HIV/AIDS publications, we took as a reference the UNAIDS (2018) definitions of geographical regions, assigning each country to its respective region as defined in that source. The regions were: North America, Western and Central Europe, Asia and Pacific, Eastern and Southern Africa, Latin America and the Caribbean, West and Central Africa, the Middle East and North Africa, and Eastern Europe and Central Asia.

Indicators obtained and analyses performed

The indicators and analyses applied in our study are structured in three blocks.

Analysis of the scientific production, research collaboration and leadership, by geographical region

As an introductory step to understanding global HIV/AIDS research, we quantified absolute scientific production by UNAIDS regions, calculating the number of documents authored by researchers from these areas. Moreover, we assessed inter-regional and international collaboration along with research leadership. The concepts used in the present study are defined as follows:

- International collaboration: joint participation in the authorship of a document by researchers from two or more countries.

- Inter-regional collaboration: joint participation in the authorship of a document by researchers from countries in two or more regions.

- Leadership: the degree of participation as the first author of documents in collaboration (number or % with respect to the total documents produced in collaboration).

Geographical affiliations were based, therefore, on authors’ institutional affiliations. The section on limitations includes an in-depth discussion on the shortcomings of this procedure, which should be considered when interpreting the results.

Analysis of research production, collaboration and leadership from countries in Africa and the Middle East

To specifically analyze HIV/AIDS research publications from African and Middle Eastern countries, we determined the number of documents authored by researchers from these countries as well as the proportion of total publications with their participation. With regard to research collaboration and leadership, the absolute and relative values on international collaboration are complemented by a specific analysis of research leadership in the top 10 most productive countries in Africa. Furthermore, a directed collaboration network was generated, representing the main African countries collaborating in global HIV/AIDS research. The nodes represent countries, and the links represent countries’ participation in the first positions of authorship. This visual representation clarifies the position that different countries occupy in the network and the collaborative links that they have established.

Subject areas and research fields in global HIV/AIDS research production

We analyzed the research subject areas and fields according to the disciplines that contributed most to scientific production on HIV/AIDS, as identified by means of the subject area classification of scientific journals in the WoS-CC as well as the MeSH descriptors and qualifiers assigned to the documents. To compare research orientations, we present data for global research output, for publications produced solely by researchers from African countries, and publications produced through collaborations between researchers from African countries and others (Africa+global collaboration). Pearson’s correlation coefficient was estimated for these three groupings to determine the affinity between African and global research production.

Finally, a co-occurrence network of MeSH terms was generated to analyze the relationships between them and to identify the specific subject areas or research orientations on HIV/AIDS in Africa and the Middle East.

Pajek and VoSViewer (Version 1.6.8, Center for Science and Technology, Leiden University) software were used to perform all processes (analysis, network generation) and obtain all descriptive indicators.

Scientific production by region and degree of international collaboration

Scientific production on HIV/AIDS is dominated by North America (which participated in 55.60% of all documents analyzed) and by Western and Central Europe (35.79%). Together, these regions participated in 82.13% of global scientific research production on HIV/AIDS that was indexed in the sources consulted. For their part, the three regions of Africa and the Middle East participated in 21.61% of the documents, albeit contributions from Eastern and Southern Africa (17.80%) were much higher than those from Western and Central Africa (3.34%) and Middle East and North Africa (1.18%) (Table  1 ). This limited scientific production contrasts with the high percentages of collaboration observed in these regions; in Eastern and Southern Africa, 82.42% of the papers were published in collaboration with authors from countries in other regions, and in Western and Central Africa, 78.39%. In contrast, 43.22% of the documents from North America were produced in inter-regional collaboration, and 47.99% from Western and Central Europe. Looking only at documents produced with inter-regional collaboration, authors from Africa and the Middle East occupied the first position on just 30 to 36% of the papers, compared to 45% for Western and Central Europe and 54% for North America (Table 1 ).

Scientific production by country and degree of international collaboration

Research production in Africa and the Middle East is concentrated in South Africa, whose researchers participated in 40.94% of the documents from these regions. At some distance are several other countries from Eastern and Southern Africa: Uganda (12.97%), Kenya (10.71%), Malawi (6.19%) and Tanzania (6.03%). Thirteen other countries show values ranging from 1.32 to 4.73%. Nigeria is the most prominent producer in Western and Central Africa, at 4.59%, while Iran leads production in the Middle East and North Africa (2.02%). Another 45 countries in Africa and the Middle East contributed to less than 1 % of the total research output (Table  2 ). Among the most productive countries (> 100 documents), Iran, Ethiopia, Nigeria, and South Africa present the lowest degree of international collaboration and the highest participation as first authors. Many of these show values of international collaboration that exceed 90%, with participation as first author under 30%. This situation is similar or even more pronounced in most low-producing countries (Table 2 ).

Generally speaking, African research output on HIV/AIDS is characterized by its cooperative links, particularly with the USA, UK, and other European countries (75 to 93% of the collaborations). However, South Africa also stands out for its intraregional ties, and it has become the main reference for research collaboration on HIV/AIDS, both in Eastern and Southern Africa and among the top 10 most productive African countries. It has collaborated with 34 different countries, led 41.44% of the collaborations, and participated in 35.76% of the papers led by other African countries. Uganda ranks second in terms of collaborative leadership within Africa, albeit with values that are much more modest, having led 14.06% of its collaborative research and participated in 11.11% of papers led by other African countries. The rest of the countries contribute less than 10% to the total collaborative links established. Except for South Africa, Uganda, and a few other countries like Zimbabwe, the collaborative links between different countries in Africa are few and far between, constituting weak and sporadic ties (Table  3 ).

Figure  2 shows a graphic representation of the collaboration network. The USA is in the center as the main reference for international collaboration on scientific output on HIV/AIDS, while the UK, Canada, and other European countries like France, Switzerland, the Netherlands, and Belgium also occupy prominent locations. South Africa is the main African reference for HIV/AIDS publications, reflecting not only its collaborations with the USA, Canada and the European countries but also its prominent role in intraregional collaborations.

figure 2

International collaboration network of research papers on HIV/AIDS with African and Middle Eastern countries (2010–2017)

Subject areas addressed in publications on HIV/AIDS in Africa and the Middle East

The correlation analysis on scientific HIV/AIDS output, produced by all countries worldwide, by African countries alone, and through Africa+global collaborations, shows differences in disciplinary orientations and research topics. In terms of disciplines involved, the lowest degree of correlation pertains to global publications versus solely African publications (k = 0.73; Table  4 ). There is also certain discordance between solely African publications and Africa+global collaborations (k = 0.79). In contrast, there is great affinity between global research output and output from Africa+global collaborations (k = 0.97). Of note, HIV/AIDS publications from Africa alone was dominated by papers in the field of “Public, Environmental & Occupational Health,” while the disciplines of “Infectious Diseases” and “Immunology” occupy the first rankings both globally and in African+global collaborations. The disciplines of “Medicine, General & Internal” and “Health Policy & Services” were also of great relevance in the publications from African countries alone (Table 4 ).

Our comparison of the MeSH qualifiers revealed similar disparities (Table  5 ). The lowest degrees of correlation were between global versus solely African research output (k = 0.68) and between global versus Africa+global collaborations (k = 0.69). However, there was a high degree of correlation between solely African publications and Africa+global collaborations (k = 0.97). With regard to the most prominent MeSH qualifiers, epidemiological studies occupy the top spot in both global and solely African publications. However, “Drug therapy” and “Therapeutic use” are more popular orientations in solely African publications than “Inmmunology,” “Genetics,” and “Metabolism” (Table 5 ).

Finally, with regard to MeSH descriptors, publications from Africa and the Middle East reflects the high prioritization of terms related to prevalence and treatment approaches (Table  6 ). Furthermore, global scientific production on HIV/AIDS suggests gender parity in terms of the research focus (both the “Male” and “Female” terms were assigned to 55% of the documents). However, for publications produced by researchers from solely African countries, the “Female” term is present in 73.38% of the documents, and for publications produced by Africa+global collaborations, this MeSH appeared in 76.71% of the documents.

Figure  3 presents a visualization of the main MeSH terms used to represent Africa and Middle East HIV/AIDS research topics and the links between them. Overall, studies that analyze anti-HIV agents, prevalence, and risk factors constitute the main subject areas that articulate the research. Incidence and its relation to sexual behaviors and health education (knowledge, prevention, acceptance of treatment for the disease) is also an important topic, as is research on pregnancy, maternal health, and prenatal care. Other relevant areas focus on co-infection (with tuberculosis, hepatitis B, hepatitis C, meningitis), resistance to anti-viral agents, and the use of certain medicines to treat the infection (lamivudine, tenofovir etc.).

figure 3

MeSH co-occurrence network on HIV/AIDS research papers from African and Middle Eastern countries (2010–2017)

Growth, visibility, and concentration of scientific production

Our analysis shows that scientific production on HIV/AIDS is still dominated by researchers from North America and Western and Central Europe, which together participated in 82% of the documents analyzed, although just 6% of people with HIV live in these regions. In contrast, researchers from countries in Africa and the Middle East participated in less than a quarter of the research papers on HIV/AIDS published between 2010 and 2017 (22%), although two-thirds of all people who are infected with the virus live there. Nevertheless, in relation to previous studies analyzing HIV/AIDS publications produced by researchers from African countries, our results indicate two highly relevant trends: (a) the notable growth in scientific production on HIV/AIDS in this region and (b) the elevated participation in scientific publications with greater visibility and international impact. In absolute terms, the number of documents we identified are double those reported by Macías-Chapula & Mijangos-Nolasco [ 8 ], based on their analysis of HIV/AIDS literature from sub-Saharan Africa included in the National Library of Medicine from 1980 to 2000, and by Uthman [ 9 ] analyzing scientific production on HIV/AIDS from sub-Saharan Africa and indexed in PubMed from 1981 to 2009.

At a country level, the advances made in research are even more significant. In their study on HIV/AIDS literature included in the National Library of Medicine, Onyancha & Ocholla [ 10 ] reported negligible contributions from Uganda and Kenya in the form of journal articles published from 1989 to 1998 ( n  = 11 and n  = 16, respectively). Our results show that these two countries have now become the second and third most productive on the continent, with a high number of contributions to journals indexed in the WoS-CC ( n  = 1921 documents from Uganda and n  = 1586 in Kenya). Uthman [ 11 ] studied HIV/AIDS research production from Nigeria between 1987 and 2006, identifying 254 articles in the WoS databases. Our findings, of 679 documents, nearly triple that number, even though the study period is substantially shorter. In South Africa, the production we identified from 2010 to 2017 ( n  = 6063) is close to that reported by Uthman [ 9 ] for the entire period from 1981 to 2009 ( n  = 8361).

Our results also show a trend toward greater research concentration, with an increase in the relative weight of high-producing countries (particularly South Africa, Uganda, and Kenya), which stand out as the main references for African scientific production on HIV/AIDS. Indeed, these countries now account for over half of all publications from Africa, and their relative contributions are trending upward. Thus, while Uthman [ 9 ] reported that South Africa participated in 34% of the HIV/AIDS publications produced by sub-Saharan Africa, in our results this figure stands at 43%. Similarly, the relative weight of Uganda and Kenya (the second and third most productive countries) has risen from 8 and 7% of the total contributions, respectively, to 14 and 11%. Similar observations have been made in other research fields [ 14 ] and particularly in the biomedical area [ 15 , 16 ], demonstrating that economic development and investments in research constitute key factors explaining the rise in scientific productivity [ 17 ].

The trend toward a greater concentration of research production in a few countries indicates the need to develop policies that facilitate a greater integration of lower-producing and less-developed countries in research activities. The literature describes some measures to stimulate research in these countries that go beyond economic investments, including training and retaining experienced researchers and fostering long-term partnerships based on equitable collaborative research ties. These strategies can enable researchers from these countries to acquire the methodological skills they need and can favor their leadership in spearheading or directing the research [ 13 ].

More specifically to the field of HIV/AIDS, Uthman [ 9 ] analyzed the factors associated with scientific productivity on HIV/AIDS in sub-Saharan Africa. His results showed that the number of people living with HIV and the number of indexed journals published in the country were predictive of an increase in publications. Other relevant factors include national scientific policies related to countries’ research agendas for this area, plus the adequate integration and participation in the system for publication and dissemination of scientific knowledge. These variables are more closely associated with scientific productivity on HIV/AIDS than others like the number of higher institutions or the number of physicians. The fact that South Africa is the country with the highest number of HIV-positive people and that this subject area has become a priority on the national research agenda [ 18 ] is clearly related to the country’s high research productivity in the field. Its economic growth has complemented this boost; together with other BRICS countries, especially China and Brazil, South Africa has laid the groundwork for development by strengthening its educational, healthcare, and social systems [ 19 , 20 ]. Increased investments in research go hand in hand with this strategy, including through establishing collaborative links with the most advanced economies at a scientific level [ 21 , 22 ]. However, as Adams et al. [ 23 ] signaled in their study, a myriad of factors affect scientific productivity and collaboration in African countries apart from structural factors like the level of economic growth or population size. For example, countries in the Commonwealth sphere, mostly situated in Eastern and Southern Africa and using English as a second language, generally present a higher level of scientific production and collaborative research than other African countries, like those in the Francophone community [ 16 ]. Our results are consistent with this trend: 10 of the 12 most productive countries are linked with the Commonwealth.

Although some countries like Nigeria or Ethiopia have made important research efforts, with corresponding increases in their scientific productivity, different studies have highlighted the need for increasing ties with neighboring countries. This would enable a more fluid exchange of knowledge and experience and foster research in key areas like detection and treatment [ 11 , 24 ].

High degree of international collaboration, low level of leadership

The two main bibliometric features we observed to be associated with HIV/AIDS research activity in Africa were: (a) a high degree of international collaboration with countries from other geographical regions, dominated by the USA and Europe (81% of the documents) and (b) a low level of research leadership, as seen through the low participation of African investigators as the first authors of documents produced in collaboration (20 to 38% among the top 10 most productive countries).

These two features may reflect a certain scientific dependence and subordination among African countries in relation to more developed countries. Moreover, the same situation has been observed in other biomedical research fields that are of special importance to the global South, like tropical diseases, infectious diseases, and pediatrics [ 22 , 25 , 26 ]. More specifically, Kelaher et al. [ 27 ] analyzed randomized controlled trials in the fields of HIV/AIDS, malaria, and tuberculosis that were undertaken in low- and middle-income countries (LMICs) from 1990 to 2013, identifying three relevant features associated with research leadership. First, there was a much higher proportion of first authors from LMICs in studies funded by LMICs (90%) than in studies funded by the USA (32%). Second, participation as first authors from LMICs was sensibly lower in the field of HIV/AIDS (33%) than for other diseases like malaria (67%). Finally, among first authors from all LMICs worldwide, those from Africa authored fewer papers than those from other regions like Latin America or Asia.

The literature describes different barriers that hinder researchers in LMICs from assuming leadership roles. Some of these are related to the absence of infrastructures or adequate financing [ 28 ]. Without an established institutional framework, stable research groups cannot be created or sustained; researchers cannot access the technical and financial support they need to submit research tenders; and coordination and monitoring of research priorities in relation to local research agendas is inadequate [ 13 , 29 , 30 , 31 ]. Other barriers have to do with deficits in methodological skills (like research design and statistical interpretation) or language (composition of articles or fluency in English). All of these factors can affect researchers’ capacity to lead studies and authorship [ 32 , 33 , 34 ].

At the same time, there are structural factors related to the hub-and-spoke model that favor the increased recognition and success of countries conducting mainstream research. Economic and human resources are concentrated in North America and Europe, and these regions also establish priority research topics. Editorial bias and the Matthew effect of accumulated advantage cement the structural forces perpetuating the under-representation of researchers from the global South from assuming positions of leadership in scientific publications [ 26 , 32 ].

The two countries constituting the axis of the collaborative research network on HIV/AIDS are the USA and South Africa. The former stands out for the high number of collaborative links it has established, with its researchers co-authoring papers with most African and Middle Eastern countries (52 countries). In total, 7693 collaborative ties (co-authored papers) were established in the study period, 70% of which were led by researchers in American institutions. Other bibliometric studies have also described the relevance of the USA in collaborative HIV/AIDS research output in Africa [ 11 ], Latin America and the Caribbean [ 35 ], and Asia [ 36 ]. Our own group have highlighted this role in other biomedical research fields [ 37 ].

For its part, South Africa is clearly the country of reference for HIV/AIDS research activity on the African continent, with a quantitative weight that is well above that observed in other biomedical areas in which it also exercises leadership. Nachega et al. [ 16 ] assessed the participation of African countries in publications on epidemiology and public health in the WoS databases, reporting that South Africa was represented in 22% of the documents, Kenya in 10%, and Nigeria in 9%. In our study, 41% of the documents on HIV/AIDS were authored by researchers in South Africa. This country, along with Ethiopia, is also notable for its leadership, figuring in the affiliations of 38% of the first authors. A similar phenomenon has also been observed in other fields of the health sciences, such as infectious diseases [ 15 , 38 ].

In addition to maintaining important collaborative ties with the USA and different European countries [ 39 , 40 ], South Africa has also emerged as a hub for intraregional collaborations within Africa. It has established links with 35 countries—far more than other African countries. Indeed, it is the main collaborator for all the other African countries in the top 10 for HIV/AIDS research productivity, even though these collaborations represent just 12% of the total collaborations in which South Africa participates. In that sense, some papers have called for BRICS countries, including South Africa, to increase their efforts to tackle the challenges primarily affecting the developing world [ 19 ]. In the case of South Africa, this could be done by promoting intraregional collaborations in sub-Saharan Africa, as research undertaken at a local level has the most potential to produce benefits, both for population health and socioeconomic development [ 20 , 41 ]. Hernandez-Villafuerte, Li & Hofman [ 42 ] analyzed collaborations among sub-Saharan countries conducting economic evaluations of healthcare interventions, reporting results consistent with ours: researchers in this region tend to collaborate more with Europeans and North Americans than with each other.

The literature highlights specific barriers impeding equitable research collaboration for African researchers, for example the paper by Okeke [ 43 ], who pointed to the limited duration of research programs, which should be longer in order to nurture stable collaborations that build hard and leadership capacities. In addition to infrastructure, other aspects mentioned include managerial expertise, administrative capabilities, and the capacity to improvise at African partner institutions. In the same line, Boum II [ 44 ] and Boum II et al. [ 45 ] discuss the difficulties in harmonizing conflicting interests between Western and African countries, making it essential to prioritize financing for equitable initiatives that lay out specific goals and expectations for partnerships, or which promote initiatives like mentorship programs and investment in Africa-based researchers that strengthen institutional capacity.

Some examples of successful collaborations for promoting equitable research partnerships and African leadership in HIV research include initiatives like the Academic Model Providing Access to Healthcare (AMPATH) in Kenya, the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium, and different initiatives coordinated and driven by the Africa Centres for Disease Control and Prevention (Africa CDC) or the Joint United Nations Programme on HIV and AIDS (UNAIDS), among others.

Research interests in public health, epidemiology, and treatment approaches

HIV/AIDS research produced by solely African countries differed from global research in terms of disciplinary and subject area orientations, with a greater focus on public health, epidemiology, and treatment. This finding indicates the need to consider regional, national, and local specificities and interests when determining research priorities. In fact, numerous studies have already signaled the poor alignment between the priorities laid out in African countries’ national research agendas and the research topics that are actually financed [ 12 , 16 , 46 , 47 , 48 , 49 ].

From a public health perspective, for example, Uthman [ 11 ] pointed out the need for further research evidence to inform HIV prevention and control programs. In this field, some countries perform better than others: South Africa is particularly strong in public health research [ 50 ], while other African countries and regions, such as French Africa, have made limited contributions [ 51 ].

Studies on epidemiology and treatment approaches for HIV/AIDS are very relevant for research produced in Africa, in contrast to what occurs on a global scale, where these orientations have a relatively limited weight. Nachega et al. [ 16 ] pointed out that research on HIV/AIDS, tuberculosis, and malaria have become the main research topics addressed in epidemiological and public health publications in African countries. However, these authors argued for moving epidemiology and public health research beyond the limited sphere of communicable disease control in order to address the regional impact of non-communicable diseases, for example in maternal and child health. This is especially relevant in the case of sub-Saharan Africa, where epidemiologists are overwhelmingly deployed to control infectious diseases, especially HIV/AIDS, tuberculosis, and malaria. The study also calls for strengthening regional expertise in epidemiology in order to shed light on the underlying causes of ill health, rather than to merely control infections and outbreaks [ 16 ].

In addition to epidemiological studies, African research also reflects an intense interest in drug therapies for HIV/AIDS, illustrating that control of the infection is a priority for research agendas and policies in African countries [ 12 ].

More specifically, previous literature on HIV/AIDS research has shown a greater focus on women in studies carried out with the participation of African researchers [ 10 ]. Our study confirms this finding: 73 to 77% of the documents investigated women, compared to 55% in the global literature. One possible explanation for this includes the fact that women are more biologically, economically, socially, and culturally vulnerable to infection. Indeed, for every 10 African men who are HIV-positive, there are 12 to 13 infected women; moreover, 55% of adults who acquire HIV are women, with profound implications for mother-to-child transmission [ 10 ]. In consonance with this fact, a greater number of women participate and work on HIV care programs in Africa, and a large proportion of the clinicoepidemiological investigations in these settings are based on care program data [ 52 ].

The different epidemiological patterns of HIV/AIDS transmission in North America and Western and Central Europe must also be taken into account, that motivate a greater interest of research in these regions on sexual transmission between men and intravenous drug users. These epidemiological patterns are less important in Africa [ 53 ]. The presence in the MeSH co-occurrence network of the descriptors “pregnancy” and “sexual behavior” are noteworthy, reflecting how African researchers are investigating aspects like maternal-fetal transmission of HIV [ 54 ] or knowledge and prevention of sexual risk, and changing the preconceptions that still persist about the social determinants of transmission [ 47 ]. The prominence of topics related to preventing mother-to-child transmission stands in contrast to the near absence of topics related to children and young people. These groups are especially sensitive to the physical and psychosocial impacts of HIV and AIDS, indicating the need for increased research on young people who are at risk of or living with HIV [ 55 ].

The greater research attention to topics related to public health, epidemiology, and treatment may also respond to limited laboratory capacity, which is needed for virologic, immunological, and basic research. In that sense, it is essential to promote initiatives that strengthen these research structures and capacities in African countries, rather than only supporting programs and projects on preventive and clinical approaches.

Limitations and future lines of research

Limitations of the present study include the fact that a considerable portion of HIV/AIDS research in African countries is disseminated using document types and media that we did not consider, such as meeting abstracts and journals that are not indexed in the WoS-CC. Moreover, using the MeSH thesaurus from the field of health sciences could have resulted in an underestimation of research spheres related to our subject area, such as research in the social sciences. In that sense, some papers have indicated that stigma and discrimination still constitute the main barriers to controlling HIV/AIDS [ 56 ]. The process used to assign geographic place variables to the papers included in the sample was based on authors’ stated institutional affiliation; this method has the inherent limitation of not being able to measure the author’s origin, nationality, or identification with the country, but rather the institution’s (and the country’s) capacity to generate outputs in the form of scientific publications. Thus, many researchers of African origin who work at institutions in the USA and Europe would be coded as US/European researchers. Furthermore, the use of first author status as a proxy for African leadership may be misleading, as an African senior author may be the last author on a publication or may have played a leadership role in some aspects other than the manuscript preparation.

Our study focused on obtaining macro indicators on scientific collaboration and output by regions and countries. Future lines of research could conduct meso- or microlevel analyses, for example focusing on the participation of institutions or authors in African HIV/AIDS research or on the impact of the publications. It would also be of great interest to identify the organisms or programs that have funded the research inspiring the publications about HIV, measuring resource contributions according to domestic versus international as well as public versus private origins.

The main conclusions of our study are as follows.

1. Our results reflect significant progress in African-produced HIV/AIDS research, at both a quantitative level (with notable increases in the number of publications) and qualitative level (through participation in journals indexed in a bibliographic database that brings together the most high-impact and high-visibility international publications). Despite these advances, however, scientific output is still concentrated in a small number of countries, chief among them South Africa, while other countries in Africa and the Middle East make only negligible contributions, despite the high burden of HIV infections.

2. The participation of African countries conducting HIV/AIDS research is characterized by a dependence on and subordination to the USA and European countries. Collaborations between these regions reflect limited leadership by African countries, as measured by the participation of African researchers as the first authors of published studies.

3. HIV/AIDS research conducted with participation from African countries shows appreciably different disciplinary and subject-area interests than global HIV/AIDS research, with a stronger focus on public health, epidemiology, and drug treatments.

It is essential to promote balanced North-South research that properly addresses the most acute needs and gaps in the places where HIV/AIDS has the largest impact. To achieve this balance, it is necessary to transfer research skills to African partners, promote equitable collaborative ties, and empower African countries, especially those with less scientific activity and more disease prevalence. In the same way, the lack of investment in research infrastructure by African governments likely makes it more difficult for African investigators to lead their own research. Intraregional collaborations among African countries can also help to avoid the further concentration of research capacity, reproducing the global North-South model on the African continent.

Availability of data and materials

The datasets generated and/or analysed during the current study are available in the Harvard Dataverse repository, https://doi.org/10.7910/DVN/RJMAY5 .

GBD 2015 HIV Collaborators. Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980–2015: the global burden of disease study 2015. Lancet HIV. 2016;3:e361–87.

Galvani AP, Pandey A, Fitzpatrick MC, Medlock J, Gray GE. Defining control of HIV epidemics. Lancet HIV. 2018;5:e667–70.

Article   PubMed   Google Scholar  

UNAIDS Data 2018. https://www.unaids.org/sites/default/files/media_asset/unaids-data-2018_en.pdf . .

Fajardo-Ortiz D, López-Cervantes M, Duran L, Dumontier M, Lara M, Ochoa H, et al. The emergence and evolution of the research fronts in HIV/AIDS research. PLoS One. 2017;12:e0178293.

Article   PubMed   PubMed Central   CAS   Google Scholar  

González-Alcaide G, Salinas A, Ramos JM. Scientometrics analysis of research activity and collaboration patterns in Chagas cardiomyopathy. PLoS Negl Trop Dis. 2018;12:e0006602.

Article   PubMed   PubMed Central   Google Scholar  

Macias-Chapula CA, Rodeo-Castro IP, Narvaez-Berthelemot N. Bibliometric analysis of AIDS literature in Latin America and the Caribbean. Scientometrics. 1998;41:41–9.

Article   Google Scholar  

Sengupta IN, Kumari L. Bibliometric analysis of AIDS literature. Scientometrics. 1991;20:297–315.

Macías-Chapula CA, Mijangos-Nolasco A. Bibliometric analysis of AIDS literature in Central Africa. Scientometrics. 2002;54:309–17.

Uthman OA. Pattern and determinants of HIV research productivity in sub-Saharan Africa: bibliometric analysis of 1981 to 2009 Pubmed papers. BMC Infect Dis. 2010;10:47.

Onyancha OB, Ocholla DN. A comparative study if the literature on HIV/AIDS in Kenya and Uganda: a bibliometric study. Libr Inf Sci. 2004;26:434–47.

Uthman OA. HIV/AIDS in Nigeria: a bibliometric analysis. BMC Infect Dis. 2008;8:19.

Mugomeri E, Bekele BS, Mafaesa M, Maibvise C, Tarirai C, Aiyuk SE. A 30-year bibliometric analysis of research coverage on HIV and AIDS in Lesotho. Health Res Policy Syst. 2017;15:21.

Chu KM, Jayaraman S, Kyamanywa P, Ntakiyiruta G. Building research capacity in Africa: equity and global health collaborations. PLoS Med. 2014;11:e1001612.

Tijssen R. Africa’s contribution to the worldwide research literature: new analytical perspectives, trends, and performance indicators. Scientometrics. 2007;71:303–27.

Uthman OA, Uthman MB. Geography of Africa biomedical publications: an analysis of 1996–2005 PubMed papers. Int J Health Geogr. 2007;6:46.

Nachega JB, Uthman OA, Ho Y-S, Lo M, Anude C, Kayembe P. Current status and future prospects of epidemiology and public health training and research in the WHO African region. Int J Epidemiol. 2012;41:1829–46.

Rahman M, Fukui T. Biomedical research productivity: factors across the countries. Int J Technol Assess Health Care. 2003;19:249–52.

Dwyer-Lindgren L, Cork MA, Sligar A, Steuben KM, Wilson KF, Provost NR, et al. Mapping HIV prevalence in sub-Saharan Africa between 2000 and 2017. Nature. 2019;570:189–93.

Article   CAS   PubMed   PubMed Central   Google Scholar  

Bai J, Li W, Huang YM, Guo Y. Bibliometric study of research and development for neglected diseases in the BRICS. Infect Dis Poverty. 2016;5:89.

Sun J, Boing AC, Silveira MPT, Bertoldi AD, Ziganshina LE, Khaziakhmetova VN, et al. Efforts to secure universal access to HIV/AIDS treatment: a comparison of BRICS countries. J Evid Based Med. 2014;7:2–21.

Bornmann L, Wagner C, Leydesdorff L. BRICS countries and scientific excellence: a bibliometric analysis of most frequently cited papers. J Assoc Inf Sci Technol. 2015;66:1507–13.

Article   CAS   Google Scholar  

González-Alcaide G, Park J, Huamaní C, Ramos JM. Dominance and leadership in research activities: collaboration between countries of differing human development is reflected through authorship order and designation as corresponding authors in scientific publications. PLoS One. 2017;12:e0182513.

Adams J, Gurney K, Hook D, Leydesdorff L. International collaboration clusters in Africa. Scientometrics. 2014;98:547–56.

Deribew A, Biadgilign S, Deribe K, Dejene T, Tessema GA, Melaku YA, et al. The burden of HIV/AIDS in Ethiopia from 1990 to 2016: evidence from the global burden of diseases 2016 study. Ethiop J Health Sci. 2019;29:859–68.

PubMed   PubMed Central   Google Scholar  

Keiser J, Utzinger J. Trends in the core literature on tropical medicine: a bibliometric analysis from 1952-2002. Scientometrics. 2005;62:351–65.

Keiser J, Utzinger J, Tanner M, Singer BH. Representation of authors and editors from countries with different human development indexes in the leading literature on tropical medicine: survey of current evidence. BMJ. 2004;328:1229–32.

Kelaher M, Ng L, Knight K, Rahadi A. Equity in global health research in the new millennium: trends in first-authorship for randomized controlled trials among low- and middle-income country researchers 1990-2013. Int J Epidemiol. 2016;45:2174–83.

Zakumumpa H, Bennett S, Ssengooba F. Leveraring the lessons learned from financing HIV programs to advance the universal health coverage (UHC) agenda in the east African community. Glob Health Res Policy. 2019;4:27.

Feldacker C, Pintye J, Jacob S, Chung MH, Middleton L, Iliffe J, et al. Continuing professional development for medical, nursing, and midwifery cadres in Malawi, Tanzania and South Africa: a qualitative evaluation. PLoS One. 2017;12(10):e0186074.

Nchinda TC. Research capacity strengthening in the south. Soc Sci Med. 2002;54:1699–711.

Wight D, Ahikireb J, Kwesigac JC. Consultancy research as a barrier to strengthening social science research capacity in Uganda. Soc Sci Med. 2014;116:32–40.

Langer A, Díaz-Olavarrieta C, Berdichevsky K, Villar J. Why is research from developing countries underrepresented in international health literature, and what can be done about it? Bull World Health Organ. 2004;82:802–3.

Smith E, Hunt M, Master Z. Authorship ethics in global health research partnerships between researchers from low or middle income countries and high income countries. BMC Med Ethics. 2014;15:42.

Yousefi-Nooraie R, Shakiba B, Mortaz-Hejri S. Country development and manuscript selection bias: a review of published studies. BMC Med Res Methodol. 2006;6:37.

Macias-Chapula CA. AIDS in Haiti: a bibliometric analysis. Bull Med Libr Assoc. 2000;88:56–61.

CAS   PubMed   PubMed Central   Google Scholar  

Chen TJ, Chen YC, Hwang SJ, Chou LF. International collaboration of clinical medicine research in Taiwan, 1990–2004: a bibliometric analysis. J Chin Med Assoc. 2007;70:110–6.

Ramos-Rincón JM, Pinargote-Celorio H, Belinchón-Romero I, et al. A snapshot of pneumonia research activity and collaboration patterns (2001–2015): a global bibliometric analysis. BMC Med Res Methodol. 2019;19:184.

Badenhorst A, Mansoori P, Chan KY. Assessing global, regional, national and sub-national capacity for public health research: a bibliometric analysis of the web of science in 1996-2010. J Glob Health. 2016;6:010504.

Falagas ME, Bliziotis IA, Soteriades ES. Eighteen years of research on AIDS: contribution of and collaborastion between different world regions. AIDS Res Hum Retrovir. 2006;22:1199–205.

Breugelmans JG, Makanga MM, Cardoso AL, Mathewson SB, Sheridan-Jones BR, Gurney KA, et al. Bibliometric assessment of European and sub-Saharan African research output on poverty-related and neglected infectious diseases from 2003 to 2011. PLoS Negl Trop Dis. 2015;9:e0003997.

Ettarh R. Patterns of international collaboration in cardiovascular research in sub-Saharan Africa. Cardiovasc J Afr. 2016;27:194–200.

Hernandez-Villafuerte K, Li R, Hofman KJ. Bibliometric trends of health economic evaluation in sub-Saharan Africa. Glob Health. 2016;12:50.

Okeke IN. Partnerships for now? Temporality, capacities, and the durability of outcomes from global health ‘partnerships’. Med Anthropol Theory. 2018;5(2):7–24.

Google Scholar  

Boum Y II. Is Africa part of the partnership? Med Anthropol Theory. 2018;5(2):25–34.

Boum Y II, Burns BF, Siedner M, Mburu Y, Bukusi E, Haberer JE. Advancing equitable global health research partnerships in Africa. BMJ Glob Health. 2018;3:e000868.

Mayosi BM, Lawn JE, van Niekerk A, Bradshaw D, Abdool Karim SS, Coovadia HM, et al. Health in South Africa: changes and challenges since 2009. Lancet. 2012;380:2029–43.

Hodes R, Morrell R. Incursions from the epicentre: southern theory, social science, and the global HIV research domain. Afr J AIDS Res. 2018;17:22–31.

Esser DE, Bench KK. Does global health funding respond to recipients’ needs? Comparing public and private donors’ allocations in 2005–2007. World Dev. 2011;39:1271–80.

Swingler GH, Pillay V, Pienaar ED, Ioannidis JP. International collaboration, funding and association with burden of disease in randomized controlled trials in Africa. Bull World Health Organ. 2005;83:511–7.

Wright CY, Dominick F, Kunene Z, Kapwata T, Street RA. Bibliometric trends of south African environmental health articles between 1998 and 2015: making local research visible and retrievable. S Afr Med J. 2017;107:915–24.

Article   CAS   PubMed   Google Scholar  

Benie-Bi J, Cambon L, Grimaud O, Kivits J, Alla F. Health needs and public health functions addressed in scientific publications in francophone sub-Saharan Africa. Public Health. 2013;127:860–6.

Nnko S, Nyato D, Kuringe E, Casalini C, Shao A, Komba A, et al. Female sex workers perspectives and concerns regarding HIV self-testing: an exploratory study in Tanzania. BMC Public Health. 2020;20(1):959.

Beyrer C, Baral SD, van Griensven F, Goodreau SM, Chariyalertsak S, Wirtz AL, et al. Global epidemiology of HIV infection in men who have sex with men. Lancet. 2012;380:367–77.

Poreau B. Prenatal diagnosis, care and management in Africa: bibliometric analysis. Pan Afr Med J. 2018;29:146.

Tran BX, Nathan KI, Phan HT, Hall BJ, Vu GT, Vu LG, et al. A global bibliometric analysis of services for children affected by HIV/acquired immune deficiency syndrome: implications for impact mitigation programs (GAPRESEARCH). AIDS Rev. 2019;21.

Sweileh WM. Bibliometric analysis of literature in AIDS-related stigma and discrimination. Transl Behav Med. 2019;9:617–28.

Download references

Acknowledgements

We gratefully acknowledge the assistance of Meggan Harris in translating our manuscript from Spanish.

Open access funding provided by University of Valencia, Special Research Actions Program (UV-19-INV-AE19).

Author information

Gregorio González-Alcaide and Marouane Menchi-Elanzi contributed equally to this work.

Authors and Affiliations

Department of History of Science and Documentation, University of Valencia, Valencia, Spain

Gregorio González-Alcaide

Department of Internal Medicine, General University Hospital of Alicante, Alicante, Spain

Marouane Menchi-Elanzi & José-Manuel Ramos-Rincón

Infectious Disease Division, Carmelo Hospital of Chókwè – Daughters of Charity, Saint Vincent of Paul, Chókwè, Gaza Province, Mozambique

Edy Nacarapa

Tinpswalo Association, Research Unit, Vincentian Association to Fight AIDS and TB, Chókwè, Gaza Province, Mozambique

Department of Clinical Medicine, Miguel Hernandez University of Elche, Alicante, Spain

José-Manuel Ramos-Rincón

You can also search for this author in PubMed   Google Scholar

Contributions

GGA: study conception, data collection, data analysis, manuscript writing and final manuscript approval; MME: study conception, data collection, data analysis, manuscript writing and final manuscript approval; NE: data analysis, manuscript writing and final manuscript approval; JMRR: study conception, manuscript writing and final manuscript approval.

Authors’ information

Two of the four authors of the present study are European (GGA and JMRR), including the first author of the study. In addition, a third author (MME) working at a European institution has signed with this affiliation. As we were aware of this imbalance, these three authors sought the collaboration of an African researcher (EN), who is from one of the most affected countries by HIV/AIDS and has extensive knowledge of the subject matter at a clinical and epidemiological level. His participation facilitated the acquisition of the methodological skills necessary for leading a study like the present one, and it strengthened our commitment to seek future collaborators enabling more balanced representation among our author teams. However, African research teams wishing to perform similar studies would likely face a range of problems, such as the lack of recognition for their research activities; time constraints due to clinical workload; and economic barriers impeding access to bibliographic databases, full-text articles for many scientific journals, translation services, and publishing costs. Indeed, although BMC “offers waivers and discounts for article processing charges (APCs) for papers whose corresponding authors are based in low-income countries,” the publication itself is only the culmination of the research process, which includes numerous processes and activities requiring economic resources or financing.

Corresponding author

Correspondence to José-Manuel Ramos-Rincón .

Ethics declarations

Ethics approval and consent to participate.

Not applicable.

Consent for publication

Competing interests.

The authors declare that they have no competing interests.

Additional information

Publisher’s note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ . The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Cite this article.

González-Alcaide, G., Menchi-Elanzi, M., Nacarapa, E. et al. HIV/AIDS research in Africa and the Middle East: participation and equity in North-South collaborations and relationships. Global Health 16 , 83 (2020). https://doi.org/10.1186/s12992-020-00609-9

Download citation

Received : 31 December 2019

Accepted : 11 August 2020

Published : 17 September 2020

DOI : https://doi.org/10.1186/s12992-020-00609-9

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

  • Scientific research
  • Human immunodeficiency virus infection
  • Acquired immune deficiency syndrome
  • African countries
  • Bibliometrics
  • International collaboration

Globalization and Health

ISSN: 1744-8603

  • Submission enquiries: Access here and click Contact Us
  • General enquiries: [email protected]

research paper on hiv/aids

U.S. flag

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

  • Publications
  • Account settings
  • Advanced Search
  • Journal List
  • Int J Environ Res Public Health

Logo of ijerph

Understanding Global HIV Stigma and Discrimination: Are Contextual Factors Sufficiently Studied? (GAP RESEARCH )

Bach xuan tran.

1 Institute for Preventive Medicine and Public Health, Hanoi Medical University, Hanoi 100000, Vietnam

2 Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21206, USA; [email protected]

Hai Thanh Phan

3 Institute for Global Health Innovations, Duy Tan University, Da Nang 550000, Vietnam; [email protected] (H.T.P.); [email protected] (H.L.T.N.)

Carl A. Latkin

Huong lan thi nguyen, chi linh hoang.

4 Center of Excellence in Behavioral Medicine, Nguyen Tat Thanh University, Ho Chi Minh City, Vietnam 700000, Vietnam; [email protected] (C.L.H.); gs.ude.sun@mchrmcp (R.C.M.H.)

Cyrus S.H. Ho

5 Department of Psychological Medicine, National University Hospital, Singapore 117599, Singapore; moc.liamg@hsohsuryc

Roger C.M. Ho

6 Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore

7 Institute for Health Innovation and Technology (iHealthtech) National University of Singapore, Singapore 117599, Singapore

Stigma and discrimination are among the greatest challenges that people living with human immunodeficiency virus (HIV) face, and both are known to negatively affect quality of life as well as treatment outcomes. We analyzed the growing research and current understanding of HIV-related stigma and contextual factors in HIV/AIDS (human Immunodeficiency virus/ acquired immunodeficiency syndrome) bibliography. A total of 5984 publications published from 1991 to 2017 were retrieved from the Web of Science database. The number of papers and their impacts have been considerably grown in recent years. Research landscapes related to stigma and discrimination include clinical, physical and mental health outcomes, risk behaviors of most-at-risk populations, and HIV-related services. We found a lack of empirical studies not only on social, cultural and economic contexts, but also on specific interventions for particular settings and sub-populations. This study highlights certain gaps and provides a basis for future studies and interventions on this critical issue given the changing drivers of HIV epidemics.

1. Introduction

According by WHO, the human immunodeficiency virus (HIV) is the virus that can destroy or impair immune system function and lead to acquired immunodeficiency syndrome (AIDS) which is known as the most advanced stages of HIV infection [ 1 ]. By the end of 2017, there were 36.9 million people living with HIV worldwide, with 1.8 million new infection cases and 940,000 deaths [ 2 ]. Therefore, HIV/AIDS is considered as a global health burden [ 3 ]. The ongoing HIV epidemic requires continued and novel strategies in order to address the biomedical and psychosocial nature of the disease [ 4 , 5 ].

Since its identification nearly 40 years ago [ 6 , 7 ], one of the toughest challenges faced by people living with HIV (PLWH) is social stigma and discrimination [ 8 ]. According to the sociologist Erving Goffman, stigma can be defined as “an attribute that links a person to an undesirable stereotype, leading other people to reduce the bearer from a whole and usual person to a tainted, discounted one” [ 9 ]. Stigma and discrimination are not only fuel the spread of epidemics, but also impact patients in their responses and living with HIV/AIDS by social isolation, stress and emotional coping, and denial of social and economic resources [ 5 , 10 ]. Despite much intensive understandings of HIV and advancements in HIV treatment, studies have recorded HIV stigma and discrimination within interpersonal, community, and healthcare environments. Discriminatory attitudes, HIV testing without consent, refusal of care and treatment, and confidentiality violation have been observed in a large number of healthcare workers [ 11 , 12 , 13 ]. A study by Wagner also reported high levels of discrimination and even overlapping stigmas held by health care providers in such a developed country as Canada [ 14 ].

Stigma and discrimination have affected PLWH’s life in many ways, and most of them are detrimental. HIV-related stigma is often associated with psychological distress, such as shame [ 15 ], depression [ 16 ], anxiety [ 17 , 18 ], suicidal ideation [ 19 ] and quality of life [ 20 , 21 , 22 ]. Furthermore, stigma towards PLWH in healthcare settings is considered one of the major barriers to optimal treatment. Numerous studies suggest that experiences of HIV-related stigma resulted in lower access to HIV treatment, low utilization of HIV care services, poorer antiretroviral therapy (ART) adherence, and thus poorer treatment outcomes [ 12 , 13 , 23 ].

Although a growing body of literature has expressed the interest in this topic, most research has focused on general issues related to HIV stigma. Marshall et al. measured the HIV-related discrimination among healthcare providers [ 13 ]. A systematic review conducted by Rueda et al. examined the associations between HIV-related stigma and health outcomes in PLWH [ 24 ]. These and other reviews provided a summary of research in this field, however, did not fully describe the trends in research and intervention designs as well as the emergence of research approaches over time. Quantifying the growth in studies and usage, which is defined as the total downloads, as well as characterizing research domains are beneficial for informing priority settings and programming, especially in a particular context. This study aims to measure the international growth in specific research interests by evaluating the tendency of research topics of published articles over time and establishing a network of research collaborations based on published literature. We also delineated the development of research landscapes for factors associated with HIV stigma and discrimination among PLWH.

2. Materials and Methods

2.1. search strategy.

A cross-sectional study for HIV/AIDS bibliography analysis was designed based on the Web of Science database. The search query of keywords consisted of HIV; human-immunodeficiency-virus, AIDS, and acquired-immune-deficiency-syndrome. We selected two types of research paper, namely research articles and research reviews, and excluded other document types (e.g., books, book chapters or data papers). The language and publication date were also restricted. The publications in English until 2017 were chosen because this study was performed in the middle of 2018. Thus, the data produced in the first half of the year may not fully reflect the trend of the entire year. The second step was to select papers mentioning stigma and discrimination in the Abstracts or Titles.

2.2. Data Extraction

Data, including authors’ names, the papers’ titles, the journals’ names, keywords, institutional affiliations, the frequency of citation, subject categories, and abstracts, were downloaded from the Web of Science database. In addition, the citation reports automatically created by the Web of Science were also downloaded. All data were converted to xlsm form (Microsoft Excel) for data checking of errors. In order to bring together the different names of an author, a process of standardization was carried out by two researchers ( Figure 1 ).

An external file that holds a picture, illustration, etc.
Object name is ijerph-16-01899-g001.jpg

Selection of papers.

2.3. Data Analysis

We analyzed data based on general characteristics (publication years, main categories, number of authors), keywords (co-occurrence keywords and most common keywords), citations, usages, and abstracts. After downloading and extracted data, we applied Macro, a programming code run on Excel, to calculate countries’ citation, intra- and inter-country collaboration. The connection among countries sharing the co-authorships was illustrated by a network graph. The author keyword co-occurrence network and countries network were also created by VOSviewer (version 1.6.8, Center for Science and Technology, Leiden University, Leiden, the Netherlands). We applied exploratory factor analysis to identify research domains emerging from all contents of the abstracts; loadings of 0.4. Jaccard’s similarity index was utilized to identify research topics or terms most frequently co-occurring with each other. It was defined as the size of the intersection divided by the size of the union of two sets of co-occurring terms. We created illustrations of the proximity values computed on all analyzed keywords using multidimensional scaling. In the map, a point represented a topic category, and the distances between pairs of items revealed to what extent those items appeared together. Colors represented the membership of specific items to different partitions created using hierarchical clustering. Stata software was used for statistical analyses. Analysis of each type of text data are presented as follows ( Table 1 ):

Type of data and analytical methods.

3.1. Number of Published Items and Publication Trend

The paper selection process is displayed in Figure 1 . Among 250,270 articles in 153 HIV related research areas, 5984 papers including the terms “stigma” or “discrimination” in the title or abstract were selected and analyzed.

The number of papers counted by study settings of 125 countries is presented in Table 2 . The American population appears to be the most well-studied one with 406 cases, accounting for 14.26% of the total sample.

Number of paper by study settings.

The increasing number of papers on discrimination towards people living with HIV/AIDS can be observed from Table 3 . Throughout the last decade, the number of papers has been considerably grown and reached 633 articles in 2017, tripling that of 2007 and making up over 15% of total HIV/AIDS studies. Notably, the total usage of the last five years of 2003 is about 3–4 times higher compared to the previous years. Total citations and usage rates have also risen remarkably, especially from 2003. Particularly, in terms of mean use rate of the last five years, the figures for the years 2003 and 2013 were the largest throughout the research period.

General characteristics of publications.

3.2. Authors and Collaborations

The global network among 97 countries having co-authorship of selected papers is illustrated in Figure 2 . The figure was constructed by counting the co-occurrence of different countries in the authors’ affiliations, and clustering them into groups of countries with similar level of co-authorship with other countries. The size of nodes is proportional to the contribution to the number of papers and the thickness of lines represents the percentage of the number of collaboration. These countries have been classified into 9 clusters of at least five countries depending on their level of international collaborations. Each color indicates a level of international co-authorship. Apart from leading nations in global HIV initiatives, such as the United States or the United Kingdom, regional neighbors or countries sharing the same languages tend to have similar levels of international co-authorship.

An external file that holds a picture, illustration, etc.
Object name is ijerph-16-01899-g002.jpg

The global networking of 97 countries having co-authorships in stigma research in HIV/AIDS.

3.3. Keywords and Research Domains

Figure 3 reveals the principal components of the keywords structure with the most frequent groups of terms. There were five major clusters emerging from 406 most frequent keywords co-occurrence of 20 times and higher. Cluster 1 (red) refers to prevention of HIV transmissions through sex or blood in particular subjects, including transgender, bisexual men, female sex workers and injecting drug users, in America, India, and Thailand. Cluster 2 (green) focuses on HIV medication adherence and associated matters in several African countries. Cluster 3 (yellow) reveals social issues relating to the mental health of young adults and homosexuals in the United States. Cluster 4 (blue) describes experiences of families having members with HIV-related chronic illnesses, while cluster 5 (purple) mentions two types of HIV/AIDS stigma, which are self-stigma and perceived stigma.

An external file that holds a picture, illustration, etc.
Object name is ijerph-16-01899-g003.jpg

Co-occurrence of most frequent author’s keywords. Note: the colors of the nodes refer to principal components of the data structure; the nodes size was scaled to the keywords’ occurrences; the thickness of the lines was drawn based on the strength of the association between two keywords.

The top 50 research domains and keywords emerged from the exploratory factor analysis of all abstracts’ contents are listed in Table 4 . Men who have sex with men, care providers, and female sex workers were the top three domains attracting greatest interest and each accounted for nearly half of total cases. Stigma and discrimination relating research domains focused on risk behaviors, clinical and quality of life outcomes, and HIV-related services uptake. Contextual factors were only found in domain # 32, which was cultural beliefs.

Top 50 research domains emerged from exploratory factor analysis of all abstracts’ contents.

Exploratory factor analysis of abstracts’ contents also emerged co-occurrence of most frequent topics ( Figure 4 ). A wide range of topics, such as outcomes of interventions, treatment and prevention, the role of social support and services, sexual transmission, and impact of discrimination and stigma, are specified in green nodes. Red nodes mention physical, psychological and social problems of people living with HIV/AIDS in general, whereas cluster in cobalt blue focuses on cross-sectional studies of the LGBT population. Brown cluster reveals the literature review of national policies and evidence of this epidemic. The remaining scatters on the right of the figure includes various issues. HIV testing and counseling, stigmatization of people living with HIV, vaccination and HIV-associated chronic diseases, for example, are the major concerns.

An external file that holds a picture, illustration, etc.
Object name is ijerph-16-01899-g004.jpg

Co-occurrence of most frequent topics emerged from exploratory factor analysis of abstracts contents.

Table 5 presents the most cited papers discussing interventions and trials related to stigma and HIV/AIDS. It depicts that the interests and preferences of the research community to approach stigma and discrimination include two main areas: (1) contextual factors including social, cultural, psycho-behaviors, gender, family and community and (2) the implementation of HIV vaccine trial.

Most cited papers mentioning interventions.

4. Discussion

This study reveals that the quantity and impacts, which are indicated by citations and usages, of publications on HIV-related stigma and discrimination have grown considerably, especially in recent years. Countries with large HIV populations, such as the United States of America, South Africa, China, India, and Uganda, possessed the highest number of empirical studies. Research landscapes related to stigma and discrimination include clinical, physical and mental health outcomes, risk behaviors of most-at-risk populations, and HIV-related services. We found a lack of empirical studies not only on social, cultural, and economic contexts but also on the design of specific interventions for particular contextual factors.

Findings from this study were in line with previous reviews in terms of factors associated with HIV-related stigma and discrimination. Previously, Sweileh published a review of 2509 papers relating to stigma and HIV/AIDS based on data obtained from Scopus database [ 25 ]. Nevertheless, the prior review simply focused on the bibliometric analysis without intensively examining research contents and scopes of the papers involved. Although similar trends in research growth and other bibliometric features were found in this research, since we quantified the factors associated with stigma and discrimination against HIV/AIDS patients and classified these factors into differential clusters, this study has enriched the understanding of current empirical research about stigma and discrimination and may help guide future studies. Specifically, media communication should expand the reach of existing interventions against the stigma of people living with HIV/AIDS. In addition, for designing interventions to reduce stigma, important context- and culture-specific factors should be incorporated into the characterization of causes of stigma. By precisely quantifying the frequency of research growth, we have incorporated a system-thinking perspective into the insights into HIV-related stigma and discrimination and have identified gaps, especially, about contextual factors, in the literature.

This study has several implications for improving HIV prevention, care, and treatment. It highlights a strong correlation between stigma and most at-risk populations, such as drug users, men who have sex with men and sex workers. In addition, as it is critical to eradicate stigma and discrimination in order to improve the access and utilization of HIV-related services [ 24 , 26 ], research on HIV-related stigma should focus more on characterizing contexts of the populations of interest, along with combining different approaches and intervention packages. An intervention, for instance, may incorporate with community-based and mass media communication to elevate its value and reduce discrimination within the population, hence, improve multiple outcomes such as mental health status, substance use, social isolation, and employment. Also, stigma and anticipated discrimination may affect patients’ quality of life due to a number of features, including family context, neighborhood, and occupation. Particularly, social judgment and stigma are highly expressed in many developing countries, where HIV epidemics mainly exist in groups exhibiting specific behaviors, such as injecting drugs and being sex workers [ 26 ]. Addressing HIV-related stigma, therefore, requires concrete empirical evidence in different contexts, which might characterize its associated factors and indicate potential effects of the interventions. Also emerged from these analyses was the association of health care services and stigma. In many circumstances, patients disclose to and seek help from health workers regarding their risk behaviors and health status. Thus, sustaining stigma reduction counseling and integrating psycho-behavioral interventions into services for PLWH may make a significant contribution to the increase of service uses and reduction of stigma against HIV-positive individuals.

Although we introduced a novel approach in summarizing and analyzing the literature, some limitations should be acknowledged. First, only publications in English were selected for this study. Another limitation is that the involved databases were limited only to the Web of Science. Despite the fact that Web of Science contains a large proportion of the literature of HIV/AIDS research, it is probably not fully representative of all data. Using the WoS database for this analysis was, however, limited in its capacity to construct indicators to describe research development. For example, we could only use the total number of downloads and the mean rates of downloads for assessing the usage. Besides, the content analysis solely consisted of abstracts instead of full texts; and the construction of different types of articles was not fully addressed in this approach of analysis. Traditionally, bibliometric analysis only focuses on number of papers and keywords instead of involving screening of abstracts because it works with a large number of papers. We enhanced the validity of such analysis by incorporating content analysis and scrutiny of abstracts in processing data. Therefore, this modified bibliometric analysis is able to put forward a comprehensive overview of research trends as well as identify gaps in the literature of the association between HIV-related stigma and contextual factors.

5. Conclusions

In conclusion, stigma and discrimination against patients with HIV/AIDS continues to be an urgent issue, given the epidemic’s dynamic nature in the extended life-long treatment. Future research and intervention will require a more intensive understanding of the impact of context as well as addressing the psycho-behavioral and social aspects of HIV care and treatment.

Author Contributions

Conceptualization, B.X.T., H.T.P., C.A.L. and R.C.M.H.; Data curation, B.X.T., H.L.T.N., C.L.H. and C.S.H.H.; Formal analysis, B.X.T., H.T.P., C.A.L., C.L.H. and R.C.M.H.; Methodology, B.X.T., H.T.P., H.L.T.N. and C.L.H.; Project administration, B.X.T.; Software, H.L.T.N. and C.L.H.; Supervision, B.X.T., C.A.L. and C.S.H.H.; Validation, H.T.P., C.A.L. and R.C.M.H.; Writing—original draft, B.X.T. and H.T.P.; Writing—review & editing, B.X.T., H.T.P., C.A.L., H.L.T.N. and C.S.H.H.

This research received no external funding.

Conflicts of Interest

The authors declare no conflict of interest.

India Today

How does HIV cause AIDS? Researchers finally have the answer

I n a groundbreaking study, University of Chicago researchers have uncovered the intricate method by which the Human Immunodeficiency Virus (HIV) infiltrates the nucleus of a cell. 

This discovery could pave the way for novel therapeutic strategies to combat the virus responsible for AIDS.

The research team, led by Arpa Hudait and Professor Gregory Voth, utilized advanced computer simulations to observe the behavior of the HIV capsid, a protein shell that encases the virus's genetic material. Their findings revealed that the capsid, which is cone-shaped, utilises its narrower end to penetrate the nuclear pore complex — a gateway into the cell's nucleus.

Contrary to previous assumptions that the capsid disassembles before or after entering the nucleus, the simulations showed that it remains intact, employing a mechanism akin to an "electrostatic ratchet" to wedge itself into the pore. 

The capsid's elasticity allows it to deform and squeeze through the opening, a process facilitated by both the flexibility of the capsid and the nuclear pore.

"This part has been a mystery for years," said Voth, the senior author of the study. "We now understand that the capsid doesn't need active work to infiltrate the nucleus; it's just physics."

The study's simulations, which are the most comprehensive of their kind, also provided insights into the nuclear pore complex itself, a critical component in various biological processes. The findings suggest that the structural design of the capsid, specifically its conical shape, is instrumental in its ability to navigate through the nuclear pore.

Each step of HIV's entry into the nucleus offers potential targets for drug development. By understanding these details, scientists can explore new ways to hinder the virus's journey and prevent infection. For instance, making the HIV capsid less elastic could impede its ability to enter the nucleus, as suggested by Hudait.

The implications of this research extend beyond HIV, offering a new perspective on how various substances gain access to the cell nucleus. "This modeling gives us a new way to understand how many things get into the nucleus, not just HIV," Voth added.

Performed at the Texas Advanced Computing Center and UChicago's Research Computing Center, this study marks a significant step forward in the fight against HIV. It not only enhances our understanding of the virus's behaviour but also opens up avenues for the development of innovative treatments that could one day lead to its eradication.

How does HIV cause AIDS? Researchers finally have the answer

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • View all journals
  • My Account Login
  • Explore content
  • About the journal
  • Publish with us
  • Sign up for alerts
  • Open access
  • Published: 12 February 2024

Income determines the impact of cash transfers on HIV/AIDS: cohort study of 22.7 million Brazilians

  • Andréa F. Silva   ORCID: orcid.org/0000-0003-4345-9797 1 , 2 ,
  • Inês Dourado 1 ,
  • Iracema Lua 1 , 2 ,
  • Gabriela S. Jesus 1 , 3 ,
  • Nathalia S. Guimarães 1 ,
  • Gabriel A. S. Morais   ORCID: orcid.org/0000-0002-6436-6314 1 ,
  • Rodrigo V. R. Anderle 1 ,
  • Julia M. Pescarini 2 ,
  • Daiane B. Machado 2 , 4 ,
  • Carlos A. S. T. Santos 2 ,
  • Maria Y. Ichihara 2 ,
  • Mauricio L. Barreto 1 , 2 ,
  • Laio Magno   ORCID: orcid.org/0000-0003-3752-0782 1 , 5 ,
  • Luis E. Souza 1 ,
  • James Macinko   ORCID: orcid.org/0000-0001-8055-5441 6 &
  • Davide Rasella   ORCID: orcid.org/0000-0002-7260-4386 1 , 2 , 7  

Nature Communications volume  15 , Article number:  1307 ( 2024 ) Cite this article

461 Accesses

3 Altmetric

Metrics details

  • Epidemiology
  • HIV infections

Living with extremely low-income is an important risk factor for HIV/AIDS and can be mitigated by conditional cash transfers. Using a cohort of 22.7 million low-income individuals during 9 years, we evaluated the effects of the world’s largest conditional cash transfer, the Programa Bolsa Família , on HIV/AIDS-related outcomes. Exposure to Programa Bolsa Família was associated with reduced AIDS incidence by 41% (RR:0.59; 95%CI:0.57-0.61), mortality by 39% (RR:0.61; 95%CI:0.57-0.64), and case fatality rates by 25% (RR:0.75; 95%CI:0.66-0.85) in the cohort, and Programa Bolsa Família effects were considerably stronger among individuals of extremely low-income [reduction of 55% for incidence (RR:0.45, 95% CI:0.42-0.47), 54% mortality (RR:0.46, 95% CI:0.42-0.49), and 37% case-fatality (RR:0.63, 95% CI:0.51 −0.76)], decreasing gradually until having no effect in individuals with higher incomes. Similar effects were observed on HIV notification. Programa Bolsa Família impact was also stronger among women and adolescents. Several sensitivity and triangulation analyses demonstrated the robustness of the results. Conditional cash transfers can significantly reduce AIDS morbidity and mortality in extremely vulnerable populations and should be considered an essential intervention to achieve AIDS-related sustainable development goals by 2030.

Introduction

Living with extremely low-income is a well-recognized risk factor for a wide range of diseases and health conditions, including HIV/AIDS 1 , 2 , which is responsible for a pandemic that caused more than 34 million deaths worldwide 3 . There is a growing consensus that HIV/AIDS control interventions should be focused not only on healthcare, but also on Social Determinants of Health (SDH), which have the potential to reduce both morbidity and mortality related to HIV/AIDS 1 , 2 , 4 . Several studies have indicated that living with low-income can contribute to the occurrence of new cases of HIV/AIDS, although wealth may also play a role in driving HIV transmission among certain populations 5 . Individuals with socioeconomic vulnerabilities are at a higher risk not only of acquiring HIV but also of encountering obstacles in accessing appropriate, timely, and continuous care and treatment. To effectively reduce the morbidity and mortality associated with AIDS, interventions need to address not only healthcare but also the SDH 6 . Moreover, HIV/AIDS reinforces the cycle of low-income perpetuation due to its frequent association with stigma, which can further exacerbate extremely low-income among populations already living in socially vulnerable circumstances 7 .

Conditional cash transfer (CCT) programs are among the most effective and widespread interventions acting on SDH and individuals living with low and extremely low-income, and they have been implemented in almost all low- and middle-income countries (LMICs) to improve the well-being of families living in precarious conditions 8 . CCT programs transfer cash to low-income households with the requirement that parents comply with specific conditions (or conditionalities), usually focused on health and education for their children. CCT programs have demonstrated positive effects on the use of preventive services, the promotion of healthy behavior, and the improvement of a wide range of health outcomes 8 . However, available research findings are still inconclusive for HIV/AIDS: 4 while some studies have shown the effects of CCTs reducing the incidence and prevalence of HIV 9 , 10 , 11 , 12 , 13 , as well as mitigating mother-to-child HIV transmission 14 , many others have found no significant impacts 15 .

In the last two decades, Brazil has implemented one of the world’s largest and more extensively evaluated CCTs, the Programa Bolsa Família (PBF) 16 . The objective of the PBF was to alleviate poverty by providing cash transfers along with educational and health-related conditions. Implemented in 2004, the program achieved nationwide coverage, with enrollment of 14.2 million families by 2018. It involved direct cash transfers from the government to low-income households, defined as families earning between US$18-36 per person per month in 2018 (at an exchange rate of 5 Brazilian real to 1 US dollar). The amount of the monthly cash benefits ranged from $17 to a maximum of $41, depending on household size and composition, with funds being deposited onto a beneficiary debit card. To continue receiving the benefits, beneficiaries were required to meet certain conditions related to healthcare and education for their children. For instance, pregnant women were expected to attend antenatal and postnatal consultations, while children were required to receive regular nutrition monitoring and vaccinations. School-aged children had to attend school. Although the program primarily focused on families with children, adult individuals living in low-income or extremely low-income without children could also qualify for and receive the benefits 16 . The large-scale and rapid increase of PBF coverage has been associated with strong nationwide reductions in poverty and social inequalities, and the improvement of several health outcomes and conditions 11 , 12 , 13 .

The success of the Brazilian response to HIV/AIDS is recognized worldwide, especially for its universalization of antiretroviral therapy (ART) in the 1990s and the current distribution of free pre-exposure prophylaxis 17 . However, the incidence of AIDS remains relatively high and unequally distributed in society 18 , with the current national rate standing at 16.5 cases per 100,000 inhabitants in 2021 19 .

To assess eligibility for social welfare programs (including PBF), Brazil has developed a large longitudinal administrative dataset corresponding to the lower-income half of its population that, linked to all nationwide AIDS-related records, has provided a unique opportunity to study the effects of CCTs on AIDS outcomes in the most vulnerable individuals – who are not usually included in epidemiological studies or randomized controlled trials.

Therefore, the aim of our study was to comprehensively evaluate the impact of CCTs on sequential AIDS outcomes – namely incidence, mortality, and case-fatality rate – using a cohort of 22.7 million Brazilians between 2007 and 2015.

The 100 Million Brazilian Cohort, the linkages, and the selection process

The selection process to achieve our final cohort, which was composed of 22,788,998 individuals between 2007 and 2015 (the period for which HIV/AIDS data were available) is described in Fig.  1 and detailed in the appendix p.3. Among the 22,788,998 individuals of the cohort, 57,99% (13,214,290) were female and 42,01% (9,574,707) male. The population under study was achieved by selecting all individuals aged 13 and older from the 100 Million Brazilian Cohort 20 , a consolidated cohort created through the linkage between the Federal Government Unified Registry for Social Programs ( Cadastro Único ) – that gathers data from the lower-income half of the Brazilian population, identifying and characterizing low-income families for social programs eligibility - and health-related datasets from the Brazilian Ministry of Health’s (appendix, p.3) 20 , 21 . Two individual-level health-related datasets were linked to the Unified Registry for Social Programs: the Notifiable Diseases Information System (SINAN) and the Mortality Information System (SIM) 22 . SINAN is a decentralized information system that monitors the incidence of notifiable diseases, including HIV/AIDS 22 . SIM is a national death surveillance system that registers deaths by all causes, including HIV/AIDS, according to CID-10 classification. The quality of each link between Unified Registry, SINAN e SIM has been extensively evaluated and validated 20 , 23 . An aggregated dataset - containing municipal-level information on AIDS endemicity levels, municipal infrastructures, and healthcare resources - was also deterministically linked to the Unified Registry through the individuals‘ municipal code of residence and baseline year.

figure 1

Flowchart of the construction of the study cohort (Brazil, 2007–2015).

During the cohort follow-up, 22,212 new AIDS cases were detected (Table  1 ): 9201 cases occurred among PBF recipients, and 13,011 among non-recipients. There were 7650 deaths from AIDS: 42.2% occurred in PBF beneficiary individuals, and 57.8% in non-beneficiaries. Among PBF non-beneficiary individuals, the AIDS incidence rate over the study period was higher (29.7/100,000 person-years) than among beneficiaries (24.9/100,000 person-years). Comparable results were found for AIDS mortality (10.1/100,000 person-years for non-beneficiary individuals and 8.7/100,000 person-years for beneficiary individuals) and case-fatality (9.3/100 person-years for non-beneficiary individuals and 6.9/100 person-years for beneficiary individuals) rates, which were higher among non-beneficiaries.

The number of AIDS cases and AIDS incidence in the study cohort (22,212) is compatible with the AIDS incidence rates in Brazil (the small difference can be explained by the age and socioeconomic composition of the cohort), as shown in Table  1 . The appendix contains additional analysis (Table  S31 , p. 46) that demonstrates the behavior of covariates between the beneficiaries and non-beneficiaries groups after applying IPTW weighting.

The IPTW multivariable regression analyses

The adjusted Rate Ratios (RR) for the associations in the total population under study, estimated using multivariable Poisson regressions and weighted by the Inverse Probability of Treatment Weight (IPTW), are presented in Table  2 (for details on the adjusted models, see the methods section). The multivariable logistic regression models used to predict the propensity scores and, consequently, the IPTW, including the odds ratios (OR) for each set of confounding variables, and each outcome, are shown in Table  S10 in the appendix. As presented in Table  2 , the receipt of PBF benefits was associated with a 41% reduction in the AIDS incidence rate (RR:0.59; 95%CI:0.57–0.61), in comparison with non-beneficiaries. Receiving PBF was also associated with a 39% reduction (RR:0.61; 95%CI:0.57–0.64) in the AIDS mortality rate and a 25% reduction (RR:0.75; 95%CI: 0.66–0.85) in the case-fatality rate. Lastly, the socioeconomic and demographic covariates showed an overall, protective effect of being female, white, having higher education, and having higher wealth. On the other hand, a greater risk was found among individuals who lived in urban areas, in houses with precarious materials and infrastructure (water supply and electric power), black, adults, and never attended school.

The PBF effect according to wealth levels, sex, and age

In the stratified analyses (Table  3 ), the associations between the receipt of PBF benefits and all AIDS indicators were considerably stronger among the extremely low-income individuals (in the 1st quartile of the distribution of the wealth variable), with statistically significant reductions of 55% in AIDS incidence (RR:0.45; 95%CI: 0.42-0.47), 54% in AIDS mortality (RR:0.46; 95%CI: 0.42-0.49), and 37% in AIDS case-fatality (RR:0.63; 95%CI: 0.51-0.76) rates. These reductions showed a consistent gradient over the levels of wealth, that is, PBF effects were progressively lower as far as the individuals have higher levels of income: for quartiles 2 (37% in AIDS incidence, 35% in AIDS mortality, and 23% in AIDS case-fatality rates) and 3 (16% in AIDS incidence, 16% in AIDS mortality, and no effect on AIDS case-fatality rates). In the 4th quartile, representing the individuals with the highest income of the study cohort (defined empirically as individuals with capita expenses - proportional to the baseline minimum wage (MW) – above 56.5%) and a negative control for our analyses 24 , PBF had no statistically significant effects. Receiving PBF benefits was also more strongly associated with a reduction in AIDS morbidity and mortality in women (of 40% in AIDS incidence, 42% in AIDS mortality, and 35% in AIDS case-fatality rates) and adolescents (of 52% in AIDS incidence, 54% in AIDS mortality).

The complete models with all covariates shown in Table  3 can be found in the appendix, pp.44–54.

Complementary, sensitivity and triangulation analyses

In the appendix (pages 38–43), we present complementary analyses that show the robustness and plausibility of our results. One significant finding is illustrated in Table  S24 , which challenges the perception that the Programa Bolsa Família (PBF) exclusively targets formal families. According to PBF eligibility rules 25 and reports 26 the beneficiaries of the program encompass a diverse range of individuals, including those in low-income or extremely low-income, whether single or in couples, even if they do not have children. Within our study cohort, only 22.7% of PBF beneficiaries are married, similar to the percentage found among the non-beneficiaries (28.7%). Additionally, the proportion of single adults is slightly higher among PBF beneficiaries (71.7%) compared to non-beneficiaries (63.7%). These percentages can be attributed to the breakdown of traditional family structures within the most impoverished communities 27 . We conducted a complementary analysis where we included marital status – not considered in the main models due to the high proportion of missing values – as an adjusting variable, showing no statistically significant differences with the main models (Table  S25 ).

As further complementary analysis, we evaluated the variable of sexual preference, available only in the dataset of People Living with AIDS (PLWA): the proportion of Men who have Sex with Men (MSM) within the PLWA cohort was accounting for 15.0% of the 26,936 PLWA individuals, suggesting that HIV transmission within this cohort of economically disadvantaged Brazilians could be in a large part due to heterosexual relationships. Furthermore, when comparing the percentage of MSM between PBF beneficiaries and non-beneficiaries within the PLWA cohort, the numbers were almost identical (Table  S26 ). Upon introducing the variable of AIDS exposure category, which includes MSM, in the assessment of PBF effects on AIDS case-fatality rates (the only analysis conducted within the PLWA cohort), the results were once again similar to the previous models, with no statistically significant differences observed (Table  S27 ). Although we were unable to adjust the models of AIDS incidence and mortality for the variable of sexual behavior (which was only available within the PLWA cohort), we can assume that it would not significantly alter the results based on the estimations mentioned earlier and the small percentage of MSM within the study cohort. While further stratification analyses of extremely vulnerable populations, such as incarcerated individuals and users of illicit drugs, have not been possible due to the lack of these variables in the study cohort, it is plausible that PBF could exert a particularly strong effect on these populations, at least of similar magnitude what have been shown in extremely low-income individuals.

The main factors attributed to the effects of PBF include increased access to the healthcare system, HIV diagnosis, prevention of AIDS progression, and treatment of AIDS (which also reduces HIV transmission in the community), as well as improved compliance to treatment due to reduced economic and geographic barriers, and improved nutritional and psychological status. In Brazil, until 2013, only AIDS cases had mandatory notification. Thus, we chose to exclude HIV notifications, which before 2013 were extremely underreported – and the main analyses were referred only to AIDS cases. However, despite these limitations and as complementary analysis, we estimated the association between the PBF exposure and the HIV cases notified in the database after 2013, and we found that receiving PBF benefits was associated to a 36% decrease in the HIV notification rate (RR: 0.64; 95% CI: 0.62–0.66) (Table  S28 ).

As shown in Fig.  2 , the gradient of effects according to the levels of wealth is extremely consistent across all HIV/AIDS indicators, as expected considering that they are sequential indicators of the progression of the disease in which poverty, and poverty-relief interventions, could act in similar ways. In Fig.  3 we show the visual comparison of the effect estimates – obtained through the adjusted IPTW Poisson regressions described above - for the four HIV/AIDS related outcomes, that is HIV notification (only starting from 2013), AIDS incidence, AIDS mortality, AIDS case-fatality (all starting from 2007), in the overall study population and in the quartiles of wealth. Moreover, the richest quartile (4 th ) shows no statistically significant effects on all indicators, demonstrating not only the robustness of the gradient but also acting as negative control for each outcome under study 24 . As a matter of fact, if the observed statistically significant associations of the PBF with HIV and AIDS-related outcomes were due to omitted variable biases, or other kind of biases related to the study design, they should have persisted in the analyses among individuals with higher income.

figure 2

Conceptual model of the potential pathways through which Programa Bolsa Familia (PBF) can affect AIDS incidence, mortality, and case-fatality rates.

figure 3

Comparison of the average effect of the Programa Bolsa Família (PBF), obtained through adjusted IPTW Poisson models with robust standard errors, on HIV notification, AIDS incidence, AIDS mortality, and AIDS case-fatality rate, 2007–2015, in the overall study population (first four lines) and by quartiles of wealth for each outcome.

To address any potential limitations in our study design, it is crucial to clarify that the assumption of the PBF rules selecting the more “motivated” individuals and leaving the vulnerable population in the “non-benefit” comparator group does not apply. This is because, as described in the methods section, the participants of this study are only individuals registered in the Cadastro Único , and after this registration process, the centralized system of the Ministry of Social Development enrolls them into the PBF based on specific eligibility rules (see methods section) with no influence during this enrollment phase of any condition or CCT conditionality 25 . Furthermore, according to our study design, all enrolled PBF beneficiaries who have received allowances are considered exposed to the PBF, even if they leave the program before the end of the study period (which occurred in 27.7% of the cases). This approach allows us to account for the post-exposure effects of PBF, but also avoid that “less motivated” individuals - who leave the program due to incompliance with PBF conditionalities – could bias our effect estimates. As a matter of fact, while a majority of individuals leave the PBF due to an increase in their income above the PBF eligibility thresholds 26 , 28 , only a small portion leaves due to non-compliance with conditionalities 29 . Nevertheless, these individuals are still considered part of the exposure group in our analysis.

To verify the robustness of the results, we systematically performed a wide range of sensitivity analyses (see the methods section and appendix p.21-33) for each outcome. First, we included different municipal-level variables, second, we tested the influence of IPTW, third, we evaluated the relevance of the endemic levels of AIDS, fourth, we tested different proxies of wealth, fifth, we fitted the same models with different specifications, including different individual-level covariates and robust standard errors, sixth, we evaluated models according to the quality of information, and finally, we evaluated the influence of missing values. Moreover, in order to verify the degree of confidence in the causal inference and in the findings of the impact evaluation, we did triangulation analyses (see appendix p. p.34-36) using alternative methodologies 30 , including survival models and propensity score matching (PSM), and all triangulation analyses indicated an high degree of confidence in the results 30 .

To the best of our knowledge, this is the largest and most comprehensive impact evaluation of the effects of a Conditional Cash Transfer program on an infectious disease, and in particular on HIV/AIDS. We were able to show the significant impact of the world’s largest CCT on all sequential AIDS-related outcomes – namely incidence, mortality and case-fatality rates - among low-income individuals in a LMIC. Moreover, similar effects were found on HIV notification. Combining big data from a nationwide cohort of 22,788,998 individuals, including 22,212 AIDS cases and 7,950 AIDS deaths over a 9-year period, with a robust quasi-experimental impact evaluation design and a wide range of sensitivity and triangulation analyses, we found a strong effect of PBF on the reduction of AIDS incidence (41%), mortality (39%) and the case-fatality rates (25%). Interestingly, the impact of the CCT was concentrated in the extremely low-income individuals of the cohort, showing a gradient of effectiveness based on the levels of socioeconomic vulnerability of the beneficiaries. Moreover, in the highest income quartile, PBF had no statistically significant effects in any of the outcomes. The impact of PBF was also stronger among women and adolescents, demonstrating the potential of CCTs in reducing health inequalities based not only on socioeconomic position, but also on sex and age.

CCT money allowances aim to promptly alleviate socioeconomic vulnerabilities, while conditionalities ensure that these families will be able to break the vicious cycle of poverty in the long term 8 , 16 . As in the large majority of CCTs, PBF conditionalities are focused on the vulnerable individuals of the family: for the health-related conditionalities pregnant women should attend all prenatal consultations, and mothers all educational activities for breastfeeding and child health, while children need to comply with the regular vaccination schedule and routine check-ups for growth and development 8 , 16 . Educational conditionalities are also focused on children, adolescents and potential young mothers, which should have a school attendance above established thresholds 8 , 16 .

Several studies have already shown that CCTs increase the use of preventive services, promote healthy behavior, and improve a wide range of health outcomes 8 . In fact, CCTs were also able to reduce the incidence of other infectious diseases, such as tuberculosis 31 , 32 and leprosy 33 , and decrease maternal and child mortality 16 . However, regarding HIV/AIDS, previous studies on the impact of cash transfers have shown inconsistent results: 4 while a randomized controlled trial in Malawi showed an HIV prevalence odd ratio of 0.36 between beneficiaries and non-beneficiaries of a cash transfer intervention for young women 10 , another randomized trial in South Africa demonstrated no statistically significant effects on HIV notification 34 . Small conditional economic rewards have also been associated to a reduction in sexually transmitted diseases in Tanzania 35 . A recent systematic review of the effects of cash transfer programs on HIV prevention suggested that cash transfers for vulnerable families may reduce risky behavior in adolescents (especially girls), but pointed out the mixed and inconsistent results from the literature, arguing for large-scale impact evaluations able to include the most vulnerable populations 4 . Regarding AIDS-related outcomes, the evidence is scarce: a randomized trial showed that incentives can promote short-term adherence at the time of HIV treatment initiation 36 , while a recent ecological observational study showed a relevant association between CCT coverage and reductions on AIDS-related hospitalizations and deaths 37 .

Our results, obtained using a number of individuals, cases, and deaths from AIDS by far larger than any other previous study, provide a possible explanation for such inconsistencies, showing that CCT impact largely depends on the baseline income levels of the beneficiaries, and it is considerably stronger for extremely low-income people in comparison with higher income individuals, among which CCT effects can even be insignificant. Moreover, our results show that CCT effects are more pronounced among women and adolescents, which have to comply with the program’s conditionalities.

CCTs have the potential to play a significant role in preventing AIDS through various mechanisms (Fig.  2 ) 4 , 8 , 10 , 34 , 37 . These mechanisms include the positive impact of increased household income and the conditionalities associated with education and healthcare that are necessary to receive the benefits. The reduction of AIDS-related morbidity and mortality can be attributed to several factors. Firstly, CCTs improve the socioeconomic conditions of families, particularly in situations of extremely low-income. By providing cash transfers, these programs can decrease the likelihood of women resorting to sex work or engaging in transactional sex for basic needs, thereby empowering them economically and enhancing their self-esteem 4 , 10 , 11 . Additionally, CCTs contribute to the reduction of risky sexual behavior, thereby preventing new cases of HIV infection and transmission 38 . The monitoring of women and children by healthcare teams and social assistance it also aids in the management of comorbidities in the late stages of AIDS, provides access to essential health information regarding treatment adherence, reduces vertical transmission, and prevents transmission to other partners 4 .

Secondly, implementing education conditionalities can have a positive impact on school enrollment and attendance, particularly for girls, thereby serving as protective measures against HIV infections 4 , 11 . Thirdly, by incorporating health conditions, such as regular prenatal and pediatric visits, these programs can encourage females to seek healthcare services and engage in sexual education activities 4 , 37 . The implementation of CCTs can also play a crucial role in slowing down or preventing the progression from HIV infection to AIDS, as well as AIDS-related deaths. By facilitating early detection and monitoring through specialized HIV/AIDS services, CCTs can address economic and geographical obstacles, enhance adherence to antiretroviral treatment, and achieve viral suppression, thereby reducing AIDS incidence, mortality rates, and HIV transmission in the general population 4 , 11 , 37 . Moreover, by granting individuals with HIV increased access to healthcare services and ensuring cost-free access to comprehensive care and ART, CCTs promote self-care and enhance adherence to treatment 37 . Furthermore, these programs alleviate food insecurity and malnutrition, both of which compromise the immune system and can hinder the transition from HIV to AIDS, as well as the effectiveness of antiretroviral treatment 37 , 39 . Our findings reinforce these ideas, as the most significant impact observed was a reduction in AIDS-related incidence and mortality rates, followed by a decrease in case-fatality rate.

Our study has limitations. Firstly, although we estimated the effect of PBF by controlling for a large number of confounding variables and using IPTW, propensity score-based models are not able to control for unobservable confounding variables. For this reason, for each outcome, we included the average municipal rate of the AIDS indicator over the period (incidence, mortality, and fatality) as an independent variable in the logistic and in the Poisson regressions, allowing adjustment for the baseline levels of the specific AIDS outcome, together with potentially associated unobservable variables. Moreover, the extended sensitivity analyses showed that the inclusion of other independent variables related to socioeconomic inequalities, healthcare services, and municipal infrastructure, did not affect the results of the PBF effect estimates (appendix, pp.22-24). Second, due to the limitations in the data sources, it was not possible to adjust for the risky sexual behaviors of the individuals. However, these risk factors should be considered mediators -and not confounders- of the PBF effects and of the social determinants included in the models, consequently, their inclusion in the regressions would lead to an over-adjustment of the models 32 , 37 .

Third, our cohort – obtained from the linkage of the Unified Registry for Social Programs with AIDS-related health records - contains data only from individuals recorded in the Unified Registry, which are part of the half of the Brazilian population with lower incomes. However, while high-income individuals are absent in our cohort, lower middle-income individuals, which need to be recorded in the Unified Registry to get access to different governmental assistance programs, are included - as shown in our stratified analyses – even if underrepresented. As a consequence, while our stratified analyses allowed to evaluate PBF effects on a wide range of different subpopulations, our overall estimates are representative of the lower income half of the country.

The main strength of our study is the combination of an extremely large longitudinal dataset with robust quasi-experimental impact evaluation methods, offering a unique opportunity to evaluate the effects of interventions with an unprecedented number of individuals and subpopulations, usually not included or underrepresented in traditional epidemiological studies and randomized controlled trials. This is particularly relevant in policy evaluation: as shown in our study, public interventions could have a very different impact according to the characteristics and baseline conditions of their beneficiaries. Another important strength of our study is the wide range of sensitivity analyses performed, which confirmed the robustness of the findings, and the use of different triangulation analyses, that demonstrate a high degree of confidence in the results of the impact evaluation.

Our study, taking advantage of a large cohort of the low-income individuals in a LMIC, was able to show how conditional cash transfer programs could significantly reduce morbidity and mortality from AIDS among socioeconomically vulnerable populations, and how their impact depends on income levels. In the current context of global increase of poverty due to consequences of the COVID-19 pandemic, the war in Ukraine, and the global inflationary surge, a strengthening and expansion of CCTs in LMICs could significantly reduce AIDS morbidity and mortality among the most vulnerable populations, and substantially contribute to the achievement of the AIDS-related Sustainable Development Goal.

Study design, population, and ethical issues

This study has a quasi-experimental cohort study design, based on the longitudinal information of 22.7 million individuals aged 13 and older, from January 1 2007 to December 31, 2015. This study was approved by the Research Ethics Committee of the Institute of Collective Health of the Federal University of Bahia (ISC/UFBA), under number 41691315.0.0000.5030 (Report No:3.783.920).

Data sources, outcomes, and intervention

The 100 Million Brazilian Cohort was based on the baseline information of families, during the period from January 1, 2001 to December 31, 2017, who sought to benefit from the Brazilian government’s social programs through registration in the Unified Registry for Social Programs (in Portuguese: Cadastro Único para Programas Sociais – Cadastro Único ). The Unified Registry is an administrative database, to which Brazilians aged 16 or over can apply by registering their personal information (age, sex, race/ethnicity, education and others) and household information (household density, familiar income, structural characteristics of the residence and others), as long as they are within one of these categories: (i) belong to a family with a monthly per capita income of up to half a minimum wage; (ii) belong to a family with a total monthly income of up to three minimum wages; (iii) belong to a family with an income greater than three minimum wages, provided that the registration is linked to inclusion in social programs in the three spheres of government; (iv) be the only resident of the household, or; (v) living on the streets (alone or with the family).

Upon registration, individuals receive a unique identifier code and are searched for socioeconomic characteristics. At the end of 2017, Unified Registry had approximately 114 million individuals on its register, which represents around 50% of the Brazilian population. It is a social tool that identifies and characterizes especially low-income families, allowing the government to know the socioeconomic aspect of the poorest and use it for the selection of social programs 20 , 40 .

Two individual-level health-related datasets were linked to the Unified Registry for Social Programs: the Notifiable Diseases Information System (SINAN) and the Mortality Information System (SIM) 22 . SINAN is a decentralized information system that monitors the incidence of notifiable diseases, including HIV/AIDS 22 . SIM is a national death surveillance system that registers deaths by all causes, including HIV/AIDS, according to CID-10 classification.

Created by the Center for Integration of Data and Knowledge for Health (CIDACS / FIOCRUZ) 20 , the Cohort aims to facilitate research and continuous assessment of social determinants and the effects of social policies and programs in health contexts in Brazil. It has 246 variables with demographic and socioeconomic information at the individual and family level. The codes and linking algorithms between the databases were built to make efficient and specific links through five identifiers: the date of birth, the municipality of residence, the sex, the name and the mother’s name of each individual presented in each of the databases 20 , 23 , 41 . The linking codes and algorithms were built based on five identifiers: date of birth, place of residence, sex, name and mother’s name of the individual present on each database 20 , 23 . The Unified Registry and the health datasets (SIM and SINAN) were individually matched in two steps, using the CIDACS-RL tool (appendix,p.3) 20 , 23 . The quality of each link between Unified Registry, SINAN e SIM has been extensively evaluated and validated 16 , 19 .

The 100 Million Brazilian Cohort resulting from this linkage has undergone several verification and consolidation processes 16 , and it has been used in various impact evaluation studies related to social determinants of health and PBF 13 , 20 . An aggregated dataset - containing municipal-level information on AIDS endemicity levels, municipal infrastructures, and healthcare resources - was also deterministically linked to the Unified Registry through the individuals‘ municipal code of residence and baseline year.

The AIDS outcomes available in the final dataset were: (i) new AIDS cases, defined by adapted CDC criteria, the Rio de Janeiro/Caracas criteria; 15 and (ii) AIDS deaths, considering as underlying cause the CID-10 codes B20 to B24 15 .

The follow-up time for each individual in the cohort, i.e., person-years, started on the date of entry into the cohort until the date of AIDS diagnosis (for AIDS incidence rate), the date of death due to AIDS (for AIDS mortality rate), or, for individuals without any AIDS-related outcome, the date of death from other causes or the end date of the cohort (December 31 2015). For AIDS case-fatality rate, the start date began with the date of diagnosis and ended with the AIDS-related death.

The beneficiary group was defined as eligible individuals who received PBF benefits [extremely low-income families are considered to have a monthly per capita income of up to US$12 (BRL 60) in 2007-2008 period, up to US$14 (BRL 70) from 2009 to 2013, and up to US$15.4 (BRL 77) in 2014 and 2015. Low-income families are those with a per capita income between US$12 (BRL 60.01) and US$24 (BRL 120) in 2007 and 2008, between US$14 (BRL 70.01) and US$28 (BRL 140) from 2009 to 2013, and between US$15.4 (BRL 77.01) and US$30.8 (BRL 154) in 2014 and 2015], and their exposure started with the receipt of the benefit, until the end of their cohort follow-up. The non-beneficiary group was defined as individuals who had never benefited from PBF throughout their follow-up period, as in previous studies 13 . In case of administrative delays and non-receipt of the benefits, eligible individuals were classified in the non-beneficiary group (details provided in the appendix p.4). Administrative delays occur because after registering with Cadastro Único and fulfilling the aforementioned requirements, the Ministry of Citizenship (in Portuguese: Ministério da Cidadania ) elects the beneficiaries of the program.

Statistical analyses

To estimate the association between PBF exposure and AIDS incidence, mortality, and case-fatality rates we used multivariable Poisson regression models, adjusted for all relevant demographic, socioeconomic, and healthcare-related confounding variables at the individual and municipal level, with follow-up time as an offset variable, robust standard errors, and observations weighted through stabilized, truncated, Inverse Probability of Treatment Weighting (IPTW). Poisson regression models with IPTW are widely used in quasi-experimental cohort studies which investigate the impacts of public and social policies on health outcomes 42 , 43 , 44 , including evaluation studies that used the 100 Million Brazilian Cohort dataset 32 , 33 .

The process of IPTW consists of two primary stages. Initially, the likelihood, also known as the propensity, of encountering the risk factor or intervention under consideration is computed based on an individual’s attributes (i.e., propensity score). Subsequently, weights are calculated as the inverse of the propensity score. By applying these weights to the study’s population, a simulated population is generated where potential sources of bias are equally balanced between the exposed and unexposed groups 45 .

We consider a scenario with two potential treatments: one involving exposure to PBF (treatment) and the other being unexposed (control). Within the potential outcomes framework, each individual is associated with a pair of potential outcomes (AIDS outcomes): \({Y}_{i}(1)\) and \({Y}_{i}(0)\) . These outcomes represent the results under the treatment and control conditions, respectively, when subjected to the same conditions 44 . However, each individual is assigned either the treatment or control, but not both. We denote \({{{{{\bf{Z}}}}}}\) as an indicator variable for treatment (exposure to PBF) ( \(Z=1\) for treatment and \(Z=0\) for control). Consequently, only a single outcome, \({Y}_{i}\) , is observable for each individual: this is the outcome linked to the actual treatment they received. The observed outcome, denoted as \({Y}_{i}\) , is determined by \({Y}_{i}={Z}_{i}{Y}_{i}\left(1\right)+\left(1-{Z}_{i}\right){Y}_{i}(0)\) . Thus, \({Y}_{i}\) is equivalent to \({Y}_{i}(0)\) if \({Z}_{i}(0)\) , and is equivalent to \({Y}_{i}(1)\) if \({Z}_{i}(1)\) 44 . Let X represent a vector of observed baseline covariates.

Initially, we used logistic regression to get the propensity score. The logistic regression equation models the probability of a binary outcome (usually 0 or 1) as a function of one or more predictor variables. The logistic function, also known as the sigmoid function, is used to transform the linear combination of predictors into the probability of the event occurring 46 , 47 .

where \(P\left(Z=1\left|\right.{{{{{\bf{X}}}}}}\right)\) is the probability of the binary outcome being 1 given the predictor variables \({{{{{\bf{X}}}}}}\) ; \(e\) is the base of the natural logarithm; \({\beta }_{0},{\beta }_{1},{\beta }_{2},\ldots,{\beta }_{p}\) are the coefficients corresponding to the predictor variables \({{{{{{\bf{X}}}}}}}_{{{{{{\bf{1}}}}}}}{{{{{\boldsymbol{,}}}}}}{{{{{{\bf{X}}}}}}}_{{{{{{\bf{2}}}}}}}{{{{{\boldsymbol{,}}}}}}\cdots{{{{{\boldsymbol{\ldots }}}}}}{{{{{{\bf{X}}}}}}}_{{{{{{\bf{p}}}}}}}.\) We estimated the probability of each individual to receive PBF (propensity score-PS), in two ways 43 , 44 , 48 . For the first equation, we calculated the marginal probability of treatment ( \({{PS}}_{t}\) ) and then we estimated the multivariable PS ( \({{PS}}_{{mul}}\) ), adjusted for all relevant covariates.

We used \({{PS}}_{t}\) and \({{PS}}_{{mul}}\) as weights to calculate the stabilized IPTW using the formulas:

where \({w}_{Z=1}\) is the weights for the beneficiaries, and \({w}_{Z=0}\) is the weights for the non-beneficiaries. In order to correct for possible extreme weights we set thresholds, with weights exceeding the set value converted to that threshold value. In this investigation, the weights were truncated based on the distribution of their values for the 1st and 99th percentiles, which represented these thresholds 43 , 44 , 48 . IPTW uses the propensity score to balance baseline characteristics in the exposed and unexposed groups by weighting each individual by the inverse probability of receiving treatment 45 .

The Poisson equation with IPTW is a framework used to analyze count data or event occurrences, while accounting for the potential bias introduced by non-random treatment assignment in observational studies. In this context, the Poisson equation models the relationship between the event outcomes and covariates while incorporating IPTW to adjust for treatment selection bias.

where \(\log ({Y}_{i})\) is the natural logarithm of the rate for individual \(i\) ; \({X}_{i1},{X}_{i2},\ldots,{X}_{{ip}}\) are the covariates for individual \(i\) ; \({\beta }_{0},{\beta }_{1},\ldots,{\beta }_{p}\) are the coefficients associated with the covariates; and \(\log ({{IPTW}}_{i})\) represents the logarithm of the inverse probability treatment weight for individual \(i\) . Finally, multivariable Poisson regressions, adjusted by stabilized, truncated IPTW, were estimated with the same socioeconomic and demographic variables adopted in the logistic model for all AIDS outcomes.

At the individual level, the demographic and socioeconomic and variables included in the models were sex, race/ethnicity, age, educational achievement, per capita expenditures used as a proxy for wealth, household characteristics (adequate water supply, household construction material, and installed electric power), geographic region, area of residence (urban and rural), and year of entry into the cohort. Due to the ART potential mediator effects in the relationship between PBF coverage and mortality from AIDS, we have also fitted the case-fatality rate models without ART as independent variable, with no changes in the PBF estimates (see appendix, Table  S30 , page 45). As municipal-level variables, we included the proportion of the population with inadequate sanitation, the unemployment rate, and a set of healthcare service-related variables (calculated as a rate per 1,000 inhabitants in the municipality): the number of doctors, nurses, and hospital beds. Lastly, in order to control for any selection bias and unobserved confounding associated with municipal endemic levels of AIDS, the average municipal AIDS incidence rate over the study period was included as a covariate in the AIDS incidence models. For mortality and case-fatality rates, we also included the municipal average AIDS mortality and case-fatality rates, respectively.

In order to investigate heterogeneity in the impact of PBF participation, the same estimation process was performed for different population strata: per capita wealth (stratified by quartile of the sum of per capita expenditure), sex, and age (adolescents and young people versus adults and the older people).

In order to assess the robustness of the results, we performed a wide range of sensitivity analyses (appendix, pp.21-36). Firstly, to evaluate the relevance of variables that capture municipal-level characteristics, we fitted models only with individual-level variables, and tested the inclusion of a wide range of different aggregate-level variables. Secondly, to understand the influence of IPTW on the PBF effect estimations, we estimated and compared all models without IPTW. Thirdly, to evaluate the influence of the inclusion of the endemic levels of AIDS in the models, we fitted the same regressions without the average municipal rates for each outcome (incidence, mortality, and case-fatality rate). Fourthly, to evaluate the adoption of per capita expenditure as a proxy of wealth, we ran the same analyses with other proxies, such as per capita income. Fifth, to evaluate the robustness of the results, we fitted the same models with different specifications, including different sets of individual-level covariates, variable distributions, and without robust standard errors, among others. Sixth, to evaluate the potential influence of low-quality information on our findings, we estimated and compared the models selecting only individuals living in municipalities with vital information of adequate quality, according to consolidated criteria 16 , 49 . Seventh, to evaluate the influence of missing values on our findings, we estimated the association of PBF for all individuals, including participants with missing data for one or more variables, both for estimating PS and adjusted Poisson models. Finally, to have a high degree of confidence in the causal inference and in the findings of the impact evaluation, we did triangulation analyses using alternative methodologies 50 , including survival models and propensity score matching (PSM).

Reporting summary

Further information on research design is available in the  Nature Portfolio Reporting Summary linked to this article.

Data availability

The protocol for the creation of the 100 Million Brazilians Cohort and the cohort profile of the 100 Million Brazilians Cohort is available in the publications referenced in the article and further material is available at: https://cidacs.bahia.fiocruz.br/en/platform/cohort-of-100-millionbrazilians . The linkage protocols are explained in the referenced publications and the codes are available at: https://gitHub.com/gcgbarbosa/cidacs-rl . However, the datasets generated during and analyzed during the current study are not publicly available due to confidentiality and ethical issues. To request access, contact us at: https://cidacs.bahia.fiocruz.br/contato/fale-conosco/ .

Code availability

The code can only be shared on request due to confidentiality and ethical issues. To request access, contact us at: https://cidacs.bahia.fiocruz.br/contato/fale-conosco/ .

Hargreaves, J. R., Davey, C. & White, R. G. Does the ‘inverse equity hypothesis’ explain how both poverty and wealth can be associated with HIV prevalence in sub-Saharan Africa? J. Epidemiol. Commun. Health (1978) 67 , 526–529 (2013).

Article   Google Scholar  

Fenton, L. Preventing HIV/AIDS through poverty reduction: the only sustainable solution? Lancet 364 , 1186–1187 (2004).

Article   PubMed   Google Scholar  

Global HIV & AIDS statistics — Fact sheet | UNAIDS. https://www.unaids.org/en/resources/fact-sheet .

Stoner, M. C. D., Kilburn, K., Godfrey-Faussett, P., Ghys, P. & Pettifor, A. E. Cash transfers for HIV prevention: A systematic review. PLoS Med . 18 , e1003866 (2021).

Article   PubMed   PubMed Central   Google Scholar  

Gillespie, S., Kadiyala, S. & Greener, R. Is poverty or wealth driving HIV transmission? AIDS 21 , S5–S16 (2007).

Peltzer, K. & Pengpid, S. Socioeconomic factors in adherence to HIV therapy in low- and middle-income countries. J. Health Popul Nutr. 31 , 150–170 (2013).

Amuri, M., Mitchell, S., Cockcroft, A. & Andersson, N. Socio-economic status and HIV/AIDS stigma in Tanzania. AIDS Care - Psychol. Socio-Med. Asp. AIDS/HIV 23 , 378–382 (2011).

Ranganathan, M. & Lagarde, M. Promoting healthy behaviours and improving health outcomes in low and middle income countries: A review of the impact of conditional cash transfer programmes. Prev. Med (Balt.) 55 , S95–S105 (2012).

Handa, S., Halpern, C. T., Pettifor, A. & Thirumurthy, H. The Government of Kenya’s cash transfer program reduces the risk of sexual debut among young people age 15-25. PLoS One 9 , e85473 (2014).

Article   PubMed   PubMed Central   ADS   Google Scholar  

Baird, S. J., Garfein, R. S., McIntosh, C. T. & Özler, B. Effect of a cash transfer programme for schooling on prevalence of HIV and herpes simplex type 2 in Malawi: A cluster randomised trial. Lancet 379 , 1320–1329 (2012).

Heise, L., Lutz, B., Ranganathan, M. & Watts, C. Cash transfers for HIV prevention: Considering their potential. J. Int. AIDS Soc. 16 , 1–5 (2013).

Guimarães, N. S. et al. The effects of cash transfer programmes on HIV/AIDS prevention and care outcomes: a systematic review and meta-analysis of intervention studies. Lancet HIV 10 , e394–403 (2023).

Richterman, A. & Thirumurthy, H. The effects of cash transfer programmes on HIV-related outcomes in 42 countries from 1996 to 2019. https://doi.org/10.1038/s41562-022-01414-7 .

Liu, J. X. et al. Conditional cash transfers to prevent mother-to-child transmission in low facility-delivery settings: Evidence from a randomised controlled trial in Nigeria. BMC Pregnancy Childbirth 19 , 1–12 (2019).

Pettifor, A. et al. The effect of a conditional cash transfer on HIV incidence in young women in rural South Africa (HPTN 068): a phase 3, randomised controlled trial. Lancet . Glob. Health 4 , e978–e988 (2016).

Google Scholar  

Rasella, D., Aquino, R., Santos, C. A. T., Paes-Sousa, R. & Barreto, M. L. Effect of a conditional cash transfer programme on childhood mortality: A nationwide analysis of Brazilian municipalities. Lancet 382 , 57–64 (2013).

Galea, J. T., Baruch, R. & Brown, B. ¡PrEP Ya! Latin America wants PrEP, and Brazil leads the way. Lancet HIV 5 , e110–e112 (2018).

BRASIL. Ministério da Saúde. Boletim Epidemiológico HIV / Aids | 2020. Secretaria de. Vigil.ância em Saúde. 1 , 68 (2020).

BRASIL- Saúde, M. da. Boletim Epidemiológico HIV / Aids | 2022. Secretaria de Vigilância em Saúde (2022).

Barreto, M. L. et al. Cohort profile: The 100 Million Brazilian Cohort. 1–12 (2021).

Unified Registry | WWP. http://wwp.org.br/en/social-policy/unified-registry/ .

DATASUS. Ministério da Saúde. https://datasus.saude.gov.br/ .

Pita, R. et al. On the accuracy and scalability of probabilistic data linkage over the Brazilian 114 Million Cohort. IEEE J. Biomed. Health Inf. 22 , 346–353 (2018).

Lipsitch, M., Tchetgen, E. T. & Cohen, T. Negative controls: a tool for detecting confounding and bias in observational studies. Epidemiology 21 , 383–388 (2010).

Lindert, K., Linder, A., Hobbs, J. & De La Brière, B. The Nuts and Bolts of Brazil’s Bolsa Família Program: Implementing Conditional Cash Transfers in a Decentralized Context . (2007).

Campello T (Organização), N. M. (Organização). BOLSA FAMÍLIA PROGRAMA BOLSA FAMÍLIA-UMA DÉCADA DE INCLUSÃO E CIDADANIA. www.ipea.gov.br . 2013 [cited 16 May 2023] .

de Cataldo, U. H. P. A família de ontem e de hoje: desagregação ou transformação? / The family of yesterday and today: breakdown or transformation? Braz. J. Dev. 5 , 5037–5050 (2019).

Mourão, L. & de Jesus, A. M. Bolsa Família (Family Grant) Programme: an analysis of Brazilian income transfer programme. http://journals.openedition.org/factsreports (2011).

Conditionalities of the Bolsa Família Program | socialprotection.org. https://socialprotection.org/discover/multimedia/conditionalities-bolsa-fam%C3%ADlia-program .

Lawlor, D. A., Tilling, K. & Smith, G. D. Approaches to causal inference Triangulation in aetiological epidemiology. Int. J. Epidemiol 1866–1886 https://doi.org/10.1093/ije/dyw314 (2016).

Nery, J. S. et al. Effect of Brazil’s conditional cash transfer programme on tuberculosis incidence. Int. J. Tuberculosis Lung Dis. 21 , 790–796 (2017).

Article   CAS   Google Scholar  

Jesus, G. S. et al. The effect of primary health care on tuberculosis in a nationwide cohort of 7·3 million Brazilian people: a quasi-experimental study. Lancet Glob. Health 10 , e390–e397 (2022).

Article   CAS   PubMed   PubMed Central   Google Scholar  

Pescarini, J. M. et al. Effect of a conditional cash transfer programme on leprosy treatment adherence and cure in patients from the nationwide 100 Million Brazilian Cohort: a quasi-experimental study. Lancet Infect. Dis. 20 , 618–627 (2020).

Pettifor, A., MacPhail, C., Nguyen, N. & Rosenberg, M. Can money prevent the spread of HIV? A review of cash payments for HIV prevention. AIDS Behav. 16 , 1729–1738 (2012).

De Walque, D. et al. Incentivising safe sex: A randomised trial of conditional cash transfers for HIV and sexually transmitted infection prevention in rural Tanzania. BMJ Open 2 , e000747 (2012).

Fahey, C. A. et al. Durability of effects from short-term economic incentives for clinic attendance among HIV positive adults in Tanzania: long-term follow-up of a randomised controlled trial. BMJ Glob. Health 6 , e007248 (2021).

de Sampaio Morais, G. A. et al. Effect of a conditional cash transfer programme on AIDS incidence, hospitalisations, and mortality in Brazil: a longitudinal ecological study. Lancet HIV 9 , e690–e699 (2022).

Ferreira-Junior, O. D. C. et al. Prevalence estimates of HIV, syphilis, hepatitis B and C among female sex workers (FSW) in Brazil, 2016. Medicine 97 , S3–S8 (2018).

Friis, H. Micronutrient interventions and HIV infection: a review of current evidence. Trop. Med. Int. Health 11 , 1849–1857 (2006).

Article   CAS   PubMed   Google Scholar  

Sanni Ali, M. et al. Administrative data linkage in Brazil: Potentials for health technology assessment. Front Pharm. 10 , 1–20 (2019).

Pinto, C. et al. Probabilistic Integration of Large Brazilian Socioeconomic and Clinical Databases. Proc IEEE Symp Comput Based Med Syst 2017-June , 515–520 (2017).

Suárez, E., Pérez, C. M., Rivera, R. & Martínez, M. N. Poisson Regression Models for Cohort Studies. Applications of Regression Models in Epidemiology 141–164 https://doi.org/10.1002/9781119212515.ch10 (2017).

Ali, M. S. et al. Propensity score methods in health technology assessment: Principles, extended applications, and recent advances. Front Pharm. 10 , 1–19 (2019).

Austin, P. C. & Stuart, E. A. Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies. Stat. Med. 34 , 3661–3679 (2015).

Article   MathSciNet   PubMed   PubMed Central   Google Scholar  

Chesnaye, N. C. et al. An introduction to inverse probability of treatment weighting in observational research. https://doi.org/10.1093/ckj/sfab158 .

Lever, J., Krzywinski, M. & Altman, N. Points of Significance: Logistic regression. Nat. Methods 13 , 541–542 (2016).

Agresti A. Categorical Data Analysis . (John Wiley & Sons., 2018).

Lee, B. K., Lessler, J. & Stuart, E. A. Weight trimming and propensity score weighting. PLoS One 6 , e18174 (2011).

Article   CAS   PubMed   PubMed Central   ADS   Google Scholar  

De Andrade, C. L. T. & Szwarcwald, C. L. [Socio-spatial inequalities in the adequacy of Ministry of Health data on births and deaths at the municipal level in Brazil, 2000-2002]. Cad. Saude Publica 23 , 1207–1216 (2007).

Lawlor, D. A., Tilling, K. & Smith, G. D. Triangulation in aetiological epidemiology. Int J. Epidemiol. 45 , 1866–1886 (2016).

PubMed   Google Scholar  

Download references

Acknowledgements

This study was supported by the US National Institute of Allergy and Infectious Diseases, National Institutes of Health (grant number 1R01AI152938). We thank the data production team and all Center for Data Integration and Knowledge in Health—FIOCRUZ collaborators for their work on building the 100 Million Brazilians Cohort. We thank our colleagues from the Collective Health Institute (Federal University of Bahia, Salvador, Brazil) for their valuable contributions during the development of the study. We acknowledge support from the grant CEX2018-000806-S funded by MCIN/AEI/ 10.13039/501100011033, and support from the Generalitat de Catalunya through the CERCA Program

Author information

Authors and affiliations.

Institute of Collective Health, Federal University of Bahia (UFBA), Salvador, Brazil

Andréa F. Silva, Inês Dourado, Iracema Lua, Gabriela S. Jesus, Nathalia S. Guimarães, Gabriel A. S. Morais, Rodrigo V. R. Anderle, Mauricio L. Barreto, Laio Magno, Luis E. Souza & Davide Rasella

Center for Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador, Brazil

Andréa F. Silva, Iracema Lua, Julia M. Pescarini, Daiane B. Machado, Carlos A. S. T. Santos, Maria Y. Ichihara, Mauricio L. Barreto & Davide Rasella

Faculty of Medicine, Federal University of Bahia (UFBA), Salvador, Brazil

Gabriela S. Jesus

Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA

Daiane B. Machado

Department of Life Sciences, State University of Bahia (UNEB), Salvador, Brazil

Departments of Health Policy and Management and Community Health Sciences, UCLA Fielding School of Public Health, Los Angeles, CA, USA

James Macinko

ISGlobal, Hospital Clinic - Universitat de Barcelona, Barcelona, Spain

Davide Rasella

You can also search for this author in PubMed   Google Scholar

Contributions

D.R., I.D. and J.M. developed the study concept. M.Y.I., M.L.B. and A.F.S. collected the data. D.R., A.F.S., I.L., J.P., G.S.J. and D.B.M. designed the study and investigation. A.F.S., D.R., I.L. and N.S.G. did the data analysis and wrote the first draft of the manuscript. C.A.S.T.S., L.M., L.E.S., G.A.S.M. and R.V.R.A. have contributed to the first draft of the manuscript. All authors contributed to data interpretation and reviewed and edited the manuscript. D.R., I.S. and J.M. supervised the study process.

Corresponding author

Correspondence to Davide Rasella .

Ethics declarations

Competing interests.

The authors declare no competing interests.

Peer review

Peer review information.

Nature Communications thanks Janaki Amin, Aaron Richterman and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. A peer review file is available.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary information, peer review file, reporting summary, rights and permissions.

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ .

Reprints and permissions

About this article

Cite this article.

Silva, A.F., Dourado, I., Lua, I. et al. Income determines the impact of cash transfers on HIV/AIDS: cohort study of 22.7 million Brazilians. Nat Commun 15 , 1307 (2024). https://doi.org/10.1038/s41467-024-44975-z

Download citation

Received : 04 September 2023

Accepted : 10 January 2024

Published : 12 February 2024

DOI : https://doi.org/10.1038/s41467-024-44975-z

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

By submitting a comment you agree to abide by our Terms and Community Guidelines . If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Quick links

  • Explore articles by subject
  • Guide to authors
  • Editorial policies

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

research paper on hiv/aids

IMAGES

  1. Research Paper Outline About HIV

    research paper on hiv/aids

  2. (PDF) The HIV Modes of Transmission model: a systematic review

    research paper on hiv/aids

  3. Role of HIV-1 Viral Load in Initiating Antiretroviral Therapy

    research paper on hiv/aids

  4. Sample Research Paper On Hiv/aids

    research paper on hiv/aids

  5. 💐 Hiv aids research paper. HIV Research Paper. 2022-10-09

    research paper on hiv/aids

  6. (PDF) HIV nursing and research

    research paper on hiv/aids

VIDEO

  1. Advances in HIV Prevention

  2. What is AIDS || HIV and it's Symptoms || Treatment of AIDS

  3. Expert analysis the latest in HIV research and clinical trials

  4. HIV Prevention and Global Health

  5. Conference looks at HIV prevention research

  6. Understanding what drives HIV

COMMENTS

  1. The emergence and evolution of the research fronts in HIV/AIDS research

    HIV/AIDS is one of the most studied infection diseases with more than 260,000 papers (mentioning the topic) listed in GOPubMed [ 2] and more than 42,000 papers (mentioning HIV/AIDS in the title) in the Web of Science [ 3] spanning over thirty year of scientific research.

  2. Four Decades of HIV/AIDS

    The dramatic saga of the acquired immunodeficiency syndrome (AIDS) features an early sense of helplessness and frustration in the face of a mysterious new disease, courage on the part of the...

  3. Research priorities for an HIV cure: International AIDS ...

    The minimal and optimal criteria for an acceptable target product profile for an HIV cure, including the duration and level of virus control off ART, has recently been developed and published by...

  4. Hiv Aids articles: The New England Journal of Medicine

    R.T. Gandhi and Others N Engl J Med 2023; 389:2468-2476 A 70-year-old woman with advanced HIV infection was evaluated because of cough, shortness of breath, and malaise. Eleven months earlier,...

  5. HIV/AIDS epidemiology, pathogenesis, prevention, and treatment

    An estimated 38·6 (33·4-46·0) million people live with HIV-1 worldwide, while about 25 million have died already. 1 In 2005 alone, there were 4·1 million new HIV-1 infections and 2·8 million AIDS deaths. 1 These estimates mask the dynamic nature of this evolving epidemic in relation to temporal changes, geographic distribution, magnitude, viral ...

  6. Extended Impact of Human Immunodeficiency Virus/AIDS Research

    The largest funder of HIV/AIDS research is the National Institutes of Health (NIH), investing nearly $69 billion in AIDS research from fiscal years 1982-2018. Despite the staggering disease burden, the scientific advances directly resulting from investments in AIDS research have been extraordinary.

  7. Experiences and Attitudes of People with HIV/AIDS: A Systematic Review

    Five topics emerged from the synthesis: feelings about the diagnosis of HIV/AIDS; stigma and HIV/AIDS; changes in sexual behavior after becoming infected; living with the virus; and pregnancy and motherhood in seropositive women.

  8. A study of awareness on HIV/AIDS among adolescents: A ...

    11 Altmetric Metrics Abstract Acquired Immunodeficiency Syndrome caused by Human Immunodeficiency Virus (HIV) poses a severe challenge to healthcare and is a significant public health issue...

  9. HIV-1 and human genetic variation

    Over the past four decades, research on the natural history of HIV infection has described how HIV wreaks havoc on human immunity and causes AIDS.

  10. HIV and AIDS: 20 years of science

    The collective output of the HIV and AIDS research community has been prodigious: more than 125,000 papers related to HIV and AIDS are catalogued in the PubMed database of the National Library of ...

  11. Reflections on 40 Years of AIDS

    The HIV/AIDS pandemic has evolved in parallel with other global health events that necessarily influence how HIV/AIDS is perceived and prioritized. In a 2012 paper, author K.D.C. suggested that global health trends could best be analyzed through the lenses of development, public health, and health security . The fourth decade of AIDS started in ...

  12. The Discovery of HIV as the Cause of AIDS

    180 Citing Articles Progress in scientific research rarely follows a straight path. Generally, it entails many unexpected meanderings, with a mix of good and bad ideas, good and bad luck. The...

  13. Research

    Research CDC provides national leadership for HIV prevention research, including the development and evaluation of HIV biomedical and behavioral interventions to prevent HIV transmission and reduce HIV disease progression in the United States and internationally.

  14. (PDF) A REVIEW ON: HIV AIDS

    DOI: License CC BY-NC-ND 4.0 Authors: Kapila A Sankalp Chaudhary Christ University, Bangalore Ram Babu Sharma Himalayan Institute of Pharmacy, Kala amb ,district sirmour , Himachal Pradesh Vashist...

  15. Current approaches to HIV vaccine development: a narrative review

    The development of an effective vaccine to protect against HIV is a longstanding global health need complicated by challenges inherent to HIV biology and to the execution of vaccine efficacy testing in the context of evolving biomedical prevention interventions.

  16. Advances in HIV/AIDS Research

    Over the past several decades, researchers have learned a lot about the human immunodeficiency virus (HIV) and the disease it causes, acquired immunodeficiency syndrome (AIDS). But still more research is needed to help the millions of people whose health continues to be threatened by the global HIV/AIDS pandemic.

  17. Ethics of HIV cure research: an unfinished agenda

    The pursuit of a cure for HIV is a high priority for researchers, funding agencies, governments and people living with HIV (PLWH). To date, over 250 biomedical studies worldwide are or have been related to discovering a safe, effective, and scalable HIV cure, most of which are early translational research and experimental medicine. As HIV cure research increases, it is critical to identify and ...

  18. AIDS Research and Treatment

    AIDS Research and Treatment publishes original research articles and review articles focused on all aspects of HIV and AIDS, from the molecular basis of the disease to translational and clinical research, prevention and education.

  19. Disruptions to HIV services due to the COVID pandemic in the USA: a

    Background The United States envisions a 90% reduction in HIV infections by 2030. However, the COVID-19 pandemic disrupted the HIV continuum and disproportionately affected access to social and health services for people at the highest vulnerability. This study shows how stakeholders in the State of Michigan handled disruptions and their key recommendations. As a case study, this study adds to ...

  20. The emergence and evolution of the research fronts in HIV/AIDS research

    In this paper, we have identified and analyzed the emergence, structure and dynamics of the paradigmatic research fronts that established the fundamentals of the biomedical knowledge on HIV/AIDS. A search of papers with the identifiers "HIV/AIDS", "Human Immunodeficiency Virus", "HIV-1" and "Acquired Immunodeficiency Syndrome" in the Web of Science (Thomson Reuters), was carried out. A ...

  21. Stigma in the HIV/AIDS epidemic: A review of the literature and

    In this paper, we systematically review the scientific literature on HIV/AIDS related stigma to document the current state of research, identify gaps in the available evidence, and highlight promising strategies to address stigma. ... Conceptual framework for HIV/AIDS related stigma. Inequalities in social, political, and economic power are the ...

  22. HIV infections

    HIV infections (human immunodeficiency virus infections) include the spectrum of infections caused by the virus HIV that range from asymptomatic seropositivity to acquired immunodeficiency...

  23. HIV/AIDS research in Africa and the Middle East: participation and

    HIV/AIDS has attracted considerable research attention since the 1980s. In the current context of globalization and the predominance of cooperative work, it is crucial to analyze the participation of the countries and regions where the infection is most prevalent. This study assesses the participation of African countries in publications on the topic, as well as the degree of equity or ...

  24. Understanding Global HIV Stigma and Discrimination: Are Contextual

    1. Introduction According by WHO, the human immunodeficiency virus (HIV) is the virus that can destroy or impair immune system function and lead to acquired immunodeficiency syndrome (AIDS) which is known as the most advanced stages of HIV infection [ 1 ].

  25. How does HIV cause AIDS? Researchers finally have the answer

    The research team, led by Arpa Hudait and Professor Gregory Voth, utilized advanced computer simulations to observe the behavior of the HIV capsid, a protein shell that encases the virus's genetic ...

  26. Income determines the impact of cash transfers on HIV/AIDS ...

    However, available research findings are still inconclusive for HIV/AIDS: 4 while some studies have shown the effects of CCTs reducing the incidence and prevalence of HIV 9,10,11,12,13, as well as ...