example of research paper about hiv

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
• Explore content
• About the journal
• Publish with us
• Sign up for alerts
• Review Article
• Published: 24 June 2021

HIV-1 and human genetic variation

• Paul J. McLaren   ORCID: orcid.org/0000-0001-6019-7018 1 , 2 &
• Jacques Fellay   ORCID: orcid.org/0000-0002-8240-939X 3 , 4 , 5  

Nature Reviews Genetics volume  22 ,  pages 645–657 ( 2021 ) Cite this article

26k Accesses

33 Citations

135 Altmetric

Metrics details

• Genetic variation

Genome-wide association studies

• Infectious diseases

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. HIV host genomic research, which aims to understand how human genetic variation affects our response to HIV infection, has progressed from early candidate gene studies to recent multi-omic efforts, benefiting from spectacular advances in sequencing technology and data science. In addition to invading cells and co-opting the host machinery for replication, HIV also stably integrates into our own genome. The study of the complex interactions between the human and retroviral genomes has improved our understanding of pathogenic mechanisms and suggested novel preventive and therapeutic approaches against HIV infection.

Similar content being viewed by others

Long COVID: major findings, mechanisms and recommendations

Hannah E. Davis, Lisa McCorkell, … Eric J. Topol

The evolutionary drivers and correlates of viral host jumps

Cedric C. S. Tan, Lucy van Dorp & Francois Balloux

Mechanisms of SARS-CoV-2 entry into cells

Cody B. Jackson, Michael Farzan, … Hyeryun Choe

Introduction

HIV-1 is the human retrovirus responsible for the HIV/AIDS pandemic, which has claimed more than 30 million lives over the past four decades. HIV infection continues to be a major global public health issue, with currently around 40 million people living with HIV (PLWH). Lifelong antiretroviral therapy (ART) has transformed the disease into a manageable chronic health condition. When available, ART enables PLWH to lead long and healthy lives but there is still no effective vaccine and no cure.

Early in the pandemic, it became clear that the risk of HIV acquisition is highly variable across humans. Socioeconomic and behavioural factors played a central role in this variability with some risk groups, such as intravenous drug users and men who have sex with men (MSM), being disproportionately affected 1 . Still, even among the most highly exposed individuals, a fraction remained HIV negative 2 , 3 . Similarly, important differences in the natural course of HIV infection (such as time from infection to AIDS diagnosis and the occurrence of opportunistic infections or malignancies) were only partially explained by known variables such as age and comorbidities 4 . Taken together, these clinical and epidemiological observations suggested a role for additional factors in the modulation of the individual response to HIV, including inherited variation in the genes and pathways involved in the retroviral life cycle and in innate or adaptative immunity against the infection.

HIV enters its main target cell, the CD4 + T lymphocyte, by binding to its receptor CD4 and to the co-receptor CC-chemokine receptor 5 (CCR5) 5 . This binding event triggers the fusion of the viral and human cell membranes, initiating a complex intracellular life cycle that will lead to the production of new viruses (Fig.  1 ). The natural immune response against HIV infection relies mostly on CD8 + T cells, also called cytotoxic T lymphocytes (CTLs). Upon primary infection, intense HIV replication results in a very high plasma viral load, measured as copies of the HIV RNA genome per millilitre of plasma, which is then partly controlled by the specific CD8 + T cell response. The very diverse human leucocyte antigen (HLA) class I molecules play a central role in this immune response by presenting small viral fragments, called epitopes , at the surface of infected cells. The recognition of these epitopes by CTL leads to the elimination of HIV-infected cells. A more efficient immune response is linked to a lower viral load during the chronic phase of an untreated infection and to slower disease progression, though it is unable to eliminate the virus 6 .

The viral envelope glycoprotein gp120 binds CD4 and CC-chemokine receptor 5 (CCR5) on the surface of target cells triggering the fusion of the viral and host cell membranes; host genomic studies have implicated genetic variants in CCR5 (purple background) listed as modifiers of infectivity. Reverse transcription of the single-stranded RNA genome into double-stranded DNA (dsDNA) occurs using proteins carried by the infecting virion. Viral dsDNA is trafficked to the nucleus, where it is integrated into the human genome. The transcription of viral dsDNA results in viral gene expression and genome replication. Viral mRNA is translated into polyproteins, which are cleaved by the viral protease. Functional proteins assemble with copies of the viral genome at the cell membrane and mature virions bud from the surface. In parallel, as part of the immune response, viral proteins are digested by the host proteasome and processed through tapasin I and II (orange rectangles) into the Golgi, where the epitopes are loaded in the human leucocyte antigen (HLA) class I molecules. The peptide-loaded HLA protein is trafficked to the cell surface and presented to cytotoxic T lymphocytes (CTLs). Variability in epitope presentation by HLA-B alleles, such as the protective allele B*57:01 , and in expression levels of HLA-C and HLA-A modify the response to infection and the set point viral load (red background). TCR, T cell receptor.

As a retrovirus, HIV can be described as a genomic pathogen. Indeed, it not only uses the molecular machinery of the infected cell for replication and dissemination but it also has the remarkable capacity to integrate a DNA copy of its RNA genome into a host cell chromosome. By becoming part of the human genome, HIV can persist in long-term cellular reservoirs for decades, making it extremely challenging to develop therapeutic strategies resulting in complete eradication 7 .

To better fight HIV infection, we must once again consider the old Delphic maxim: ‘know thyself’. Because HIV is an expert at hijacking human cells and immunity, we have no choice but to improve our understanding of our inner machinery, starting with the most fundamental layer of biological information — the human genome. The exploration of human diversity at the DNA level, long hampered by technological limitations, has been fuelled by the development of new and more powerful tools over the past decades 8 . Thanks to progress in our understanding of human genetic diversity, in genotyping and sequencing technology, as well as in bioinformatics and data science, it became possible to search for genetic factors that modulate the individual response to HIV, including the resistance and susceptibility to infection and the natural history of the disease in PLWH 9 .

In this Review, we first present an overview of the technological and conceptual developments that have fuelled HIV host genomic research. We then describe the major genetic factors modulating the natural history of HIV infection — in the HLA class I region and the CCR5 locus. Next, we highlight the recent convergence of human and HIV genomics, which allows longitudinal analyses of host–pathogen genetic interactions. Finally, we explain how genomic knowledge is poised to have a positive impact on PLWH, notably through pharmacogenomic interventions and stratification of care based on polygenic risk scores (PRS) before discussing the short-term and long-term perspectives for translational research and clinical applications of human genomics in the field of HIV.

Discovering host genetic variants

The search for human genetic differences that have an impact on HIV-related outcomes was first motivated by clinical observations, namely the striking variability in individual trajectories of patients in the absence of treatment. It was further propelled by a desire to uncover fundamental physiopathological mechanisms by the careful exploration of genomic variants and their impact on host and viral molecular processes.

Candidate gene studies

In the candidate gene approach, population-level associations are sought between HIV-related phenotypes and specific genetic variants in genes that have been selected based on previous biological knowledge or functional work. The selected variants are typically typed using targeted genotyping assays or Sanger sequencing of the region of interest. This framework was first applied to HIV host genetics in the early 1990s in analyses of allelic variants in genes known or suspected to play a role in HIV pathogenesis or in the antiretroviral immune response. Therefore, genetic associations were reported in two broad categories: genes coding for proteins involved in the HIV life cycle (such as PPIA 10 and TSG101 (ref. 11 )) and immune-related genes encoding molecules implicated in innate and adaptive immune pathways (such as MBL2 (ref. 12 ) and TLR9 (ref. 13 )) as well as in specific antiretroviral defence mechanisms (such as APOBEC3G 14 and TRIM5 (ref. 15 )). Dozens of genes were tested in multiple cohorts. Unfortunately, as has been the case in the broader field of human genetics, most reported associations turned out to be false positives, notably owing to the small sizes of the studied cohorts, population stratification and the lack of correction for multiple testing. Replication attempts in larger cohorts, where these factors could be better controlled, showed no association for the vast majority of variants 16 , 17 , 18 . In fact, only two major discoveries remain from the candidate gene era: the protective effect of a homozygous 32 bp deletion in CCR5 ( CCR5Δ32 ) against HIV acquisition 19 , 20 , 21 and the modulating effect of HLA alleles on HIV progression for which early studies, largely in MSM of European ancestry in the United States, noted a strong impact of the HLA-B alleles B*57 and B*27 on delaying time to AIDS onset 22 .

Advances in genotyping and sequencing technologies progressively transformed human genetic analyses during the first decade of this century. In particular, the commercial availability of genome-wide genotyping arrays marked the beginning of the era of genome-wide association studies (GWAS). The principle of a GWAS is to simultaneously test very large numbers of genetic variants throughout the genome for potential associations with a phenotype of interest 23 . This truly agnostic approach finally allowed for a more comprehensive exploration of the human genome. To date, most GWAS have been based on the genotyping of single nucleotide polymorphisms (SNPs) followed by imputation, a process that leverages the linkage disequilibrium property of the human genome to statistically infer the genotypes that are not directly measured. This approach allows near-comprehensive testing of common variants (that is, variants with a minor allele frequency of >1%) in most human populations 24 .

The first GWAS of any infectious disease focused on the level of detectable viral genetic material in the blood of untreated, chronically infected individuals during the period of HIV latency 25 . This phenotype, known as set point viral load (spVL), was selected because of its relative ease of measurement and its known correlation to the rate of progression to AIDS 26 and transmission potential 27 . The spectrum of interrogated variants was limited by early DNA genotyping arrays, yet genome-wide significant associations were identified in the HLA class I region, the most polymorphic locus in the human genome, known to have a crucial role in the modulation of T cell immunity (see ‘HLA variation in HIV control’, below). These findings were soon validated and expanded by other GWAS performed in independent cohorts, which demonstrated that the genetic architecture of HIV spVL is comparable between the general population of PLWH 16 , 28 , 29 , 30 and a particular group of individuals able to maintain low viral loads for prolonged periods of time in the absence of ART, the so-called HIV controllers 17 , 31 . The absence of specific genetic factors explaining the HIV controller phenotype was a disappointment in terms of potential therapeutic development. However, it is consistent with what has been found for many complex human traits and diseases — that individuals at the extremes of the phenotypic distribution are more likely to carry multiple common variants with weak effects rather than rare, high-impact variants 32 . Beyond genotyping, a single exome sequencing study has been published so far in the HIV field 33 also indicating that rare coding variants with large effect sizes are unlikely to make a major contribution to host control of HIV infection.

GWAS were less successful in the search for determinants of HIV resistance, with no definitive evidence found of human genetic polymorphisms conferring an altered susceptibility to HIV apart from CCR5 variation 18 , 34 . However, recent genome sequencing studies of extreme exposure phenotypes 35 have shown promising associations in CD101 , a gene encoding an immunoglobulin superfamily member implicated in regulatory T cell function 36 , and in UBE2V1 , which encodes a ubiquitin-conjugating enzyme involved in pro-inflammatory cytokine expression 37 , 38 that associates with the HIV restriction factor TRIM5α 38 . Although both CD101 and UBE2V1 are plausible candidates, further functional studies are required to validate their role in HIV susceptibility. Finally, analyses of GWAS data provide evidence for residual heritability owing to additive genetic effects beyond CCR5 (ref. 18 ) and genetic overlap with behavioural and socioeconomic traits 39 . These results suggest that larger genomic studies of HIV acquisition may identify additional loci that impact susceptibility and warrant further investigation, potentially in large biobanks.

Several intrinsic limitations make it difficult to investigate the genetic mechanisms potentially involved in HIV resistance. For example, sample sizes are usually small (in the tens or hundreds) because studies need to be performed on highly exposed yet uninfected individuals such as patients with haemophilia exposed to HIV through contaminated blood products 34 , sex workers in hyper-endemic areas 40 or serodiscordant couples (stable heterosexual couples where one partner has HIV infection and the other is seronegative for HIV at enrolment) 29 . Frailty (or survival) bias is a limitation in cross-sectional studies of HIV cohorts with long-term follow-up, as these cohorts are enriched for genetic factors protecting against HIV disease progression. Another limitation is misclassification bias in studies comparing the genomes of patients with HIV infection to unselected controls from the general population, in which most individuals are in fact susceptible to HIV infection 18 . The identification of additional genetic determinants of individual susceptibility to HIV infection will require increased sample sizes (ideally in the thousands) as well as the use of sequencing approaches to characterize the rare functional variants that are not interrogated in studies based on genotyping arrays.

HLA variation in HIV control

The hla locus in infectious diseases.

The human major histocompatibility complex (MHC) located on chromosome 6 is one of the most genetically diverse loci in the genome 41 . The extended MHC occupies ~7.6 Mb of the human genome 42 and encodes more than 400 genes, many of which are key mediators of the innate and adaptive immune responses. Within this locus, alleles at the classical class I ( HLA-A , HLA-B , HLA-C ) and class II ( HLA-DR , HLA-DQ , HLA-DP ) genes have been associated with numerous autoimmune, inflammatory and infectious diseases (reviewed in refs 43 , 44 ) with recent preprints demonstrating extensive disease associations in large biobanks from multiple populations 45 , 46 . In the context of infectious disease, class I HLA proteins present endogenous peptides on the surface of infected cells for recognition by CTLs, triggering the development of an adaptive response. As discussed below, the variability in epitope specificity of HLA proteins and expression levels of HLA class I alleles has a dramatic impact on the progression of HIV disease.

Effects of amino acid variability encoded by HLA alleles

An individual’s genotype at class I HLA genes has been consistently demonstrated to be the major host genetic determinant of HIV spVL and rate of disease progression across geographic contexts and ancestries 17 , 22 , 47 , 48 , 49 , 50 . This observation was put in the genome-wide context by the first GWAS of HIV spVL 25 and HIV controllers 17 that exclusively identified SNPs in strong linkage disequilibrium with classical HLA-B alleles. Although array-based techniques for the genotyping of DNA samples do not allow for the direct resolution of classical HLA alleles, computational methods leveraging linkage disequilibrium structure between SNPs and sequence-based HLA types in reference populations allow for accurate imputation of classical HLA types from GWAS data 51 . The application of this technique to a sample of >6,000 PLWH of European ancestry underscored the dramatic effect of HLA-B*57:01 on reducing viral load, which was, on average, ~0.8log10 RNA copies/ml lower in individuals carrying this allele 52 . This study also demonstrated strong associations at multiple other classical class I HLA alleles that had a range of effects, from decreasing spVL ( B*57:01 , B*27:05 , B*13:02 , B*14:02 , C*06:02 , C*08:02 , C*12:02 ) to increasing spVL ( B*07:02 , B*08:01 , C*07:01 , C*07:02 , C*04:01 ).

To better understand how functional variation in HLA class I proteins can impact HIV spVL, recent studies have tested variable amino acid positions within these proteins to fine-map the classical allele associations. In a GWAS performed by the International HIV Controllers study, this technique was applied to demonstrate that previously identified associations between HIV control and classical HLA alleles such as B*57:01 could be explained by variability across a small number of amino acid positions within the HLA-B protein 17 . The strongest effect was observed at position 97 of the protein, which accommodates six alternative amino acids, including valine, which is unique to B*57 haplotypes. A recent preprint describing the comprehensive analysis of the impact of HLA amino acid polymorphisms on spVL in a multi-ethnic sample of >12,000 PLWH identified three amino acid positions in HLA-B (positions 67, 97 and 156) and one in HLA-A (position 77) as independently associating with spVL 53 . The positions within HLA-B map to classical HLA alleles known to impact spVL, whereas the HLA-A position suggests that HLA-A functions independently of HLA-B. Interestingly, all four positions are located in the peptide-binding groove of the respective HLA protein, supporting the hypothesis that epitope presentation is key for the natural suppression of HIV replication. Furthermore, there was no substantial evidence that the effects of these polymorphic positions differed across ancestry groups, suggesting biological relevance across global contexts.

Several mechanisms of action have been proposed to explain why different alleles of the same HLA gene have differential effects on HIV progression. Studies of epitope specificity have shown that certain protective alleles, including B*57:01 (which uniquely carries valine at position 97) and B*27:05 (which carries the protective cysteine and asparagine residues at positions 67 and 97, respectively), drive compensatory mutations in the HIV genome leading to reduced viral fitness 54 , 55 , 56 . In addition to differential epitope specificity, the CTL effector function induced by epitope presentation has been implicated in HIV control, with CTLs in carriers of some protective HLA alleles exhibiting an enhanced proliferative capacity and more polyfunctional responses 57 , 58 , 59 .

Within-host diversity and epitope presentation

In addition to the impact of specific class I HLA alleles on HIV progression at the population level, the within-host diversity of HLA alleles may be important at the individual level. An early study looking at the impact of allele combinations revealed that maximum heterozygosity at HLA class I genes (that is, individuals carrying two different alleles at all three class I genes) was associated with a reduced time to AIDS 47 . This observation was supported by a GWAS that showed that individuals carrying different HLA alleles at each class I gene had a significantly lower viral load than homozygous individuals, even after accounting for the additive effect at each allele 60 . This heterozygote advantage likely comes from the ability to present multiple HIV epitopes, supporting the hypothesis that the breadth of presentation is beneficial in preventing HIV progression. To further test this hypothesis, a recent in silico study used novel algorithms to predict the binding affinity of all possible 9-mer peptides in the HIV proteome to HLA proteins encoded by the different class I alleles 61 . Coupling these predicted affinities to clinical and genetic data demonstrated that spVL was negatively correlated with the breadth of the peptide repertoire bound by an individual’s HLA protein isoforms. Moreover, HLA-B isoforms had the largest predicted breadth of epitope recognition and conferred the strongest reduction of viral load (Fig.  2a ). However, the quantity of epitopes alone is unlikely to fully explain the protective capacity of an individual’s HLA alleles, as subsets of epitopes that are uniquely presented by protective HLA isoforms explained more of the observed variance in spVL than the entire predicted set. This observation is further supported by an in silico and functional study that demonstrated that HIV epitopes that encode structurally important residues are preferentially targeted by protective HLA isoforms and associate with elite control of replication 62 . Thus, the quantity and quality of HIV epitopes presented by combinations of HLA isoforms are the key drivers of spVL.

a | HIV-infected cells expressing protective HLA-B alleles tend to present a more diverse and more structurally conserved set of HIV epitopes compared to non-protective alleles. Interactions with protective alleles tend to produce a more polyfunctional cytotoxic T lymphocyte (CTL) response. b | HLA-C protein isoforms vary broadly in their level of expression on the surface of infected cells. HLA-C alleles that do not have a binding site for microRNA-148a (miRNA-148a) in the 3′ untranslated region of their mRNAs escape suppression and present more peptide on the cell surface than alleles with an miRNA-148a binding site, resulting in the initiation of stronger CTL responses. c | Different HLA-A alleles express different amounts of HLA-A signal peptide, which positively correlates with HLA-E peptide expression. HLA-E interacts with the NKG2A receptor on the surface of natural killer (NK) cells and, when highly expressed, inhibits the killing of infected cells.

Non-classical effects of HLA variation

In addition to the classical effects of HLA genes on peptide presentation, several studies have suggested that non-classical effects may play a part in limiting HIV replication in vivo. In particular, the variable expression levels of classical HLA-C alleles have been linked to HIV control, with those expressed at high levels conferring protection against disease progression 63 . This effect has been observed across ancestries and has been linked to the absence of a variable microRNA-148a (miR-148a) binding site in the 3′ untranslated region of HLA-C 64 . The proposed model suggests that mRNA from alleles lacking the miR-148a binding site escape suppression by miR-148a; as a consequence, proteins encoded by these alleles and loaded with HIV epitopes are expressed at higher levels on infected cells, allowing for greater rates of detection by CTLs 64 (Fig.  2b ). Similarly, proteins encoded by HLA-A alleles are also expressed at variable levels on the cell surface 65 . However, in contrast to HLA-C , HLA-A alleles expressed at high levels associate with poorer control of viral replication and with faster disease progression 66 . A combination of genetic and functional studies indicated that increased HLA-A expression levels correlated with higher viraemia in a combined cohort of more than 9,000 PLWH from sub-Saharan Africa and the United States. It was proposed that this effect may be the result of enhanced production of the HLA class I signal peptide that regulates HLA-E expression, a hypothesis that was supported by a correlation between HLA-A expression and HLA-E expression among 58 healthy donors tested 66 . HLA-E is a ligand for natural killer group protein 2A (NKG2A) and their interaction results in strong inhibition of natural killer (NK) cell degranulation (Fig.  2c ). Thus, the enhanced production of the HLA class I signal peptide in individuals carrying highly expressing HLA-A alleles may lead to enhanced inhibition of immune responses in infected individuals, resulting in poorer clinical outcomes.

Finally, it has also been observed that the combination of HLA genotype and the expression of particular killer cell immunoglobulin-like receptor (KIR) proteins variably modulated HIV disease course 67 . The KIR proteins are a highly variable set of cell-surface receptors expressed on NK cells (and some T cells) that, when engaged by their cognate receptors, either activate or inhibit NK cell-mediated killing (recently reviewed in ref. 68 ). In particular, the combination of the activating KIR3DS1 allele with a set of HLA-B alleles that carry isoleucine in the Bw4 epitope (Bw4-I80) is highly associated with HIV control 69 . Taken together, these results demonstrate the complex interplay between epitope presentation, HLA protein expression and NK inhibition.

CCR5 variation in HIV infection

Ccr5δ32 and resistance against hiv infection.

Perhaps the most highly touted example of human genetic variability restricting infectious diseases is the observation that individuals carrying two copies of a loss-of-function variant in the gene encoding the cell receptor CCR5 are highly resistant to infection by HIV. CCR5 is a chemokine receptor expressed on the surface of multiple subsets of monocytes and lymphocytes, including CD4 + T cells, the major HIV target cells . At the earliest stages of infection, the HIV envelope protein gp120 binds CD4 and CCR5 on the cell surface, resulting in fusion of the viral and host cell membranes and in the release of the viral genome into the target cell. The discovery that individuals who carry homozygous loss-of-function alleles at CCR5 are resistant to infection was first made in a group of MSM that were multiply exposed to the virus but remained uninfected 19 . It was determined that these men all shared a 32-bp deletion in the CCR5 gene (the CCR5Δ32 allele) that leads to the production of a non-functional protein and the absence of functional CCR5 on the cell surface prevents HIV from entering target cells (Fig.  3a ). The CCR5Δ32 allele is observed at ~10% frequency in individuals of European ancestry (homozygosity occurs at a frequency of 1%), at a reduced frequency in southern Europeans compared to those in the north 70 and is not observed at an appreciable frequency in other continental populations. Compound heterozygotes (that is, individuals carrying one copy of CCR5Δ32 and a second loss-of-function CCR5 variant) are also resistant to infection, although these individuals are exceedingly rare 71 .

a | A 32-bp deletion in CCR5 ( CCR5Δ32 ) results in the reduced expression of CC-chemokine receptor 5 (CCR5) on the surface of target cells. Heterozygous individuals exhibit reduced CCR5 expression, lower set point viral loads (spVLs) and slower disease progression. Individuals carrying two defective copies of the CCR5 gene show no surface expression and are highly resistant to HIV infection. Additionally, rs1015164, a single nucleotide polymorphism downstream of CCR5 , affects cell surface levels of CCR5. In homozygous reference (A/A) and heterozygous (A/G) individuals, the surface expression of CCR5 is normal, whereas G/G homozygous individuals have a lower CCR5 surface expression and lower spVLs. b | rs1015164 regulates the expression of an antisense RNA termed CCR5-AS. When CCR5-AS (orange) is expressed at high or intermediate levels in homozygous reference (A/A) and heterozygous (A/G) individuals, respectively, CCR5 mRNA (blue) is protected from RALY-mediated degradation and results in normal levels of surface expression. In G/G homozygous individuals, CCR5-AS expression is diminished and CCR5 mRNA is degraded, resulting in lower surface expression at the cellular level and a lower spVL overall. lncRNA, long non-coding RNA.

The observation that individuals lacking CCR5 expression are resistant to HIV infection directly led to the development of the antiviral drug Maraviroc, a CCR5 antagonist 72 , as well as to the world’s first ethically fraught attempt at human embryo engineering 73 . Perhaps most interestingly, bone marrow transplants between CCR5Δ32 homozygous donors and recipients with HIV infection have resulted in the only two confirmed cases of long-term HIV cure 74 , 75 . Although promising, this effect has been difficult to replicate in engineered autologous stem cell models 76 and is unlikely to be scalable to the level necessary to stem the pandemic. Additionally, the protection is not absolute, as several confirmed cases of infection in CCR5Δ32 homozygotes have been reported (reviewed in ref. 77 ), presumably by viruses that utilize the minor co-receptor CXCR4 or by dual-tropic viruses.

Associations between CCR5 variation and spontaneous HIV control

In addition to the impact of homozygosity on preventing infection, individuals with a single CCR5Δ32 copy exhibit lower spVL and delayed disease progression compared to those with two functional copies 19 , 20 , 78 , likely because the reduced levels of CCR5 protein on the cell surface lower the efficiency of HIV entry into target cells (Fig.  3a ). The CCR5 locus was also identified in GWAS, first in a study of ~2,500 PLWH in Europe 16 and then in an expanded set of 6,300 individuals from across the globe 52 . However, the CCR5Δ32 allele was not directly assayed on the genotyping platforms used in these studies, thus only proxy SNPs were identified. In a combined analysis of GWAS data and direct CCR5Δ32 genotyping, it was observed that the CCR5Δ32 allele was not the most strongly associated variant in the region, suggesting that multiple independent genetic effects occur at this locus. Conditional analysis accounting for the effect of CCR5Δ32 showed that an additional marker, rs1015164, was also strongly associated with spVL. Functional analysis of this variant showed that it regulates the expression of an antisense long non-coding RNA called CCR5-AS , which overlaps the CCR5 gene 79 . This study further showed that the increased expression of CCR5-AS resulted in increased CCR5 expression because CCR5-AS interfered with the RALY-mediated degradation of CCR5 mRNA. Moreover, the knockdown of CCR5-AS reduced the susceptibility of CD4 + T cells to HIV-1 infection ex vivo (Fig.  3b ). These results demonstrate that the clinical course of untreated HIV infection is directly influenced by the innate level of CCR5 expression within the infected individual. Whether additional functional polymorphisms in CCR5 have similar effects remains an open question.

Host and pathogen genetic variation

Pathogen sequence variation as an indicator of host genetic pressure.

Most studies performed so far in the field of host genetics focused on clinically defined outcomes such as the susceptibility to infection or disease progression. However, intermediate phenotypes have been shown to be very valuable in identifying subtle genetic association signals that are not always detectable using more complex clinical outcomes. A particularly promising intermediate phenotype, unique by its nature to infectious diseases, is variation in the pathogen genome (Fig.  4 ). HIV is a highly variable virus that establishes a lifelong infection. Therefore, it represents an ideal model to search for the potential effects of intra-host selective pressure on a human pathogen. While some of the variants observed in the HIV genomic sequence are present in the transmitted/founder virus , another fraction is acquired during the course of the disease resulting, at least partially, from the selective pressure exerted by the host response to infection. Signs of host-driven selection are clearly visible in the HIV genome. In particular, specific variants have been described in key viral epitopes presented by HLA class I molecules and targeted by CTL responses 80 . Mutations have also been reported in regions targeted by KIR, suggesting the escape from immune pressure by NK cells 81 , 82 . A non-negligible fraction of the HIV-1 genome (~12%) is under positive selection but only about half of the positively selected sites map to canonical CD8 + T cell epitopes 83 , indicating that additional host factors could be driving evolution in non-epitope sites.

First, genetic variants in the host (human) and pathogen (viral) genomes are identified from genome-wide genotyping or sequencing data and catalogued. A genome-wide search for associations between human polymorphisms and viral variants is then performed, which needs to consider the risk of systematic signal inflation owing to population stratification. On the human side, this can be addressed by methods that infer genetic ancestry, such as principal component (PC) analysis followed by the inclusion of the top PCs as covariates, or by the use of mixed models that incorporate the full covariance structure of the study population 130 . On the pathogen side, various phylogenetic-based and model-based approaches have been proposed 85 . Significant associations, after correction for multiple testing, reveal the loci involved in host–pathogen genomic conflicts. The plot showing the signatures of viral–host interactions is adapted from ref. 84 , CC BY 3.0 ( https://creativecommons.org/licenses/by/3.0/ ).

Genome-to-genome studies

Computational approaches developed over the past decade have allowed more comprehensive analyses of the reciprocal genetic signals resulting from the host–pathogen interaction 84 , 85 . Joint analyses of human and HIV sequence variation start with the generation of large-scale genomic data from paired samples. The retroviral genome can be isolated and sequenced either as native RNA during replicative infection or as proviral DNA, integrated into the host genome, during latent infection. Human genomic information can be obtained using genotyping or sequencing technology. The principle of genome-to-genome (G2G) studies is then to perform a systematic search for associations between human genetic polymorphisms and viral sequence variants, at the nucleotide or amino acid levels. Because of the very large number of models run in parallel — one GWAS for each viral variant — this approach requires stringent correction for multiple testing. By mapping all interacting loci, G2G studies have the potential to uncover the most important genes and pathways involved in specific responses to infectious agents, thereby revealing novel diagnostic or therapeutic targets. In addition to identifying the sites of genetic interplay between virus and host, this study design makes it possible to estimate the biological consequences of such interactions and to estimate the relative impact of human and viral genetic variation on phenotypic outcomes by assessing associations between human-driven escape at viral sites and a quantitative clinical phenotype. In spite of these promises, it must be acknowledged that G2G studies have not led, as of today, to the identification of novel HIV restriction factors in the human genome 86 . Future studies will require larger sample sizes to increase power but also more diversity with a strong focus on the inclusion of PLWH of non-European ancestries.

Nevertheless, studies based on the combined analysis of host and pathogen genomic variation have already demonstrated their potential in other infections. In particular, the use of a similar study design in chronic hepatitis C virus infection highlighted the evolutionary pressure exerted by both innate (interferon-λ) and acquired (HLA class II) immune defence mechanisms 87 , 88 . The intra-host evolution of DNA viruses can also be investigated using a G2G approach, as shown in a recent study that revealed several associations between human and Epstein–Barr virus sequence variation in immunosuppressed PLWH 89 .

HIV precision medicine

Expanding antiretroviral therapy to eradicate hiv.

With the now accepted knowledge that PLWH who do not have detectable plasma viral loads cannot transmit the virus to others 90 , the Joint United Nations Programme on HIV/AIDS (UNAIDS) set an ambitious 90–90–90 target 91 , where 90% of infected people know their status, 90% of those are on antiviral therapy and 90% of those are suppressing the virus below the level of detection. This aspirational treatment target would practically mean, given currently available technologies, that more than 34 million people would be on lifelong chemotherapy. Although this treatment as prevention approach would undoubtedly result in decreases in transmission and dramatic increases in life expectancy for the population with HIV infection, it also requires a deeper understanding of how human genetic variation relates to variability in drug toxicity and response to long-term therapy.

HIV pharmacogenetics

In addition to affecting HIV disease progression in untreated individuals, human genetic variability has also been implicated in modifying the response to treatment. A major achievement in the fight against HIV has been the development of multiple, effective therapeutics that target several stages of the viral life cycle. These include entry inhibitors, which prevent the binding of the viral spike protein gp120 to host cell receptors and fusion of the virus with host cell membranes; nucleoside and non-nucleoside reverse transcriptase inhibitors, which prevent the reverse transcription of the viral RNA genome into DNA; integrase inhibitors, which prevent the integration of the viral DNA product into the host genome; and protease inhibitors, which prevent the cleavage of viral polyproteins into their functional subunits (Fig.  5 ). For several classes of anti-HIV therapy, human genetic variability is known to influence response to the drug, which in some cases leads to severe adverse events and treatment discontinuation 92 . Paradoxically, the HLA-B allele B*57:01 , most notably associated with the control of infection, also predisposes carriers to a severe hypersensitivity reaction to the nucleoside reverse transcriptase inhibitor abacavir 93 , 94 ; the high specificity binding of abacavir alters the binding pocket of HLA-B*57:01 and triggers reactivity to self-peptides 95 . Similarly, variants in genes encoding the drug-metabolizing enzymes CYP2B6 (refs 96 , 97 , 98 ), CYP2A6 (ref. 99 ), CYP2C9 (ref. 100 ), CYP2C19 (ref. 100 ), CYP3A 101 and ABCC2 (ref. 101 ) have all been associated with slow metabolization kinetics of their cognate drugs (Table  1 ), in some cases leading to drug accumulation in the brain, psychiatric complications and treatment stoppage 99 . The frequency of many of these polymorphisms varies depending on ancestral background, leading to reduced drug tolerance and therefore reduced efficacy in some populations. For example, the allele CYP2B6*6 (rs3745274), which results in the slow metabolism of efavirenz and nevirapine, two non-nucleoside reverse transcriptase inhibitors recommended for first-line use by WHO until recently, has an approximately twofold higher frequency in some African populations compared to Europeans 102 . This increased frequency and the resulting adverse events led to thousands of cases of treatment discontinuation in Zimbabwe when the nation adopted a single-pill efavirenz-containing regimen 103 . This example highlights the need to not only tailor the therapy to the individual but, in some cases, to the population as well. Newer generations of HIV therapies, such as integrase inhibitors and advanced nucleoside reverse transcriptase inhibitors, have more favourable pharmacokinetic and safety profiles 104 . However, the effects of long-term treatment with these drugs and any potential interactions with human genetic variability remain to be understood.

Commonly used antiretroviral drugs target receptor binding, reverse transcription, integration and protease cleavage. Genetic variation in several human genes (in bold) have been shown to modify drug metabolism and contribute to adverse drug reactions (Table  1 ). CCR5, CC-chemokine receptor 5.

Complex trait genomics in HIV medicine

In addition to the direct interactions between host genotype and drug metabolism, patients on long-term HIV therapy also experience early onset of several chronic diseases, including cardiovascular disease 105 , 106 , 107 , metabolic syndrome 108 , kidney disease 109 , 110 and liver fibrosis 111 . These conditions are all known to have high heritability in the HIV uninfected population and genetic risk factors for type 2 diabetes mellitus 112 and cardiovascular disease 113 have been shown to be enhanced in PLWH on therapy. Recently, there has been a push to develop PRS in the general population. These scores, built by summing the additive effects of dozens to thousands of genetic variants within an individual, have been shown to have a strong predictive ability for multiple metabolic, inflammatory, tumoural and cardiovascular conditions 32 . Investigations of PRS in the specific context of HIV infected individuals receiving long-term antiretroviral therapy have just begun, with the recent demonstrations that the prediction of chronic kidney disease can be improved through the addition of a PRS to the known clinical and pharmacological risk factors 114 , 115 and that a PRS can be useful to stratify PLWH at a high risk of cardiometabolic diseases who may benefit from preventive therapies 116 . An important caveat is that PRS are not necessarily transferable across ancestral groups and, as in all areas of genomics, attention should be paid to enhancing diversity and ensuring equity in precision medicine approaches.

Conclusion and future perspectives

Host genomic studies have advanced our understanding of HIV biology in several important ways. Firstly, the demonstration of the dominant impact of HLA variation on HIV progression in the context of the whole genome reinforced the need to focus on T cell responses in vaccine design. Moreover, the ability to accurately infer HLA allele types and protein-level variability from genotyping array data, an approach first piloted in HIV genomic studies, has greatly increased our understanding of how amino acid variability in HLA molecules contributes to multiple medically important traits. Secondly, dense genotyping and large sample sizes enabled the discovery of multiple, independent signals in the CCR5 locus, which provided a deeper understanding of how the expression of CCR5 is regulated and how it modulates HIV infection beyond the known impact of the CCR5Δ32 allele. Finally, amassing genome-wide data for large cohorts of PLWH has enabled the validity of previous candidate gene associations to be assessed, providing a new standard for identifying novel loci of HIV restriction.

In recent years, there have been several barriers to further advancing our understanding of how host genomics affects HIV susceptibility and progression. Firstly, current studies have predominantly included individuals of European ancestry, mirroring the lack of diversity in genomics in general 117 , which is particularly problematic because the vast majority of PLWH are non-White. The example of the population-specific CCR5Δ32 allele further highlights the need to stretch beyond European cohorts to determine if other population-specific effects may exist. Attaining the large sample sizes required for genomic discovery in non-European populations will require a substantial investment of resources and building of capacity in low-income and middle-income countries. Furthermore, understanding the potential function of genetic variants identified in diverse samples will require a shift towards inclusivity across genomics databases 118 . Secondly, with improvements in HIV care and broad adoption of test and treat strategies, the focus of host genomics studies has necessarily shifted away from the natural history of infection phenotypes to intermediate phenotypes, pharmacogenomics of long-term therapy, comorbidities or vaccine response. Thirdly, understanding other classes of genetic variation that are not well captured by genotyping arrays, for example, diversity of KIR alleles and T cell receptor usage, the other partner in the HLA interaction, should be investigated to better understand how genetic variation in key innate and adaptive immune genes impact disease outcomes. However, capturing these types of variation requires in-depth sequencing to resolve genetic diversity and, in the case of T cell receptor variation, targeted immune assays to capture the relevant cells. Progress on computational methods for inferring variation at some complex loci from genotyping array data 51 , 119 or next-generation sequencing data 120 , 121 , 122 will greatly aid these efforts.

The full translational potential of host genomics discovery in HIV has yet to be realised. Although the association between HLA allele type, epitope binding and HIV control have been well established, this knowledge has yet to be translated into an effective preventative or therapeutic vaccine. As mentioned above, treatment of PLWH with CCR5-deficient cells has shown potential as an HIV cure but several technological improvements in autologous cell editing will be required before it becomes a scalable strategy. In addition to targeting host genes for editing, in vitro studies have also shown that it is feasible to directly target and excise the integrated proviral genome 123 , 124 . Although an extremely promising strategy, the delivery of the necessary machinery to latently infected cells remains a challenge.

The host genomics approach established in HIV research has since been applied to several other infectious diseases, including those posing substantial threats to human health such as hepatitis C virus 125 , 126 , tuberculosis 127 , malaria 128 and even SARS-CoV-2 (ref. 129 ), among others. These studies have time and again uncovered novel therapeutic targets and mechanisms to identify the individuals who are most vulnerable to specific infections. As the world struggles with a novel pandemic-causing RNA virus, the lessons we can learn from how the human genome contributes to variability in outcome have never been more important.

Friedland, G. H. & Klein, R. S. Transmission of the human immunodeficiency virus. N. Engl. J. Med. 317 , 1125–1135 (1987).

Article   CAS   PubMed   Google Scholar  

Kulkarni, P. S., Butera, S. T. & Duerr, A. C. Resistance to HIV-1 infection: lessons learned from studies of highly exposed persistently seronegative (HEPS) individuals. AIDS Rev. 5 , 87–103 (2003).

PubMed   Google Scholar  

Horton, R. E., McLaren, P. J., Fowke, K., Kimani, J. & Ball, T. B. Cohorts for the study of HIV-1-exposed but uninfected individuals: benefits and limitations. J. Infect. Dis. 202 (Suppl. 3), S377–S381 (2010).

Article   PubMed   Google Scholar  

Sabin, C. A. & Lundgren, J. D. The natural history of HIV infection. Curr. Opin. Hiv. AIDS 8 , 311–317 (2013).

PubMed   PubMed Central   Google Scholar  

Chen, B. Molecular mechanism of HIV-1 entry. Trends Microbiol. 27 , 878–891 (2019).

Article   CAS   PubMed   PubMed Central   Google Scholar  

Letvin, N. L. & Walker, B. D. Immunopathogenesis and immunotherapy in AIDS virus infections. Nat. Med. 9 , 861–866 (2003).

Dufour, C., Gantner, P., Fromentin, R. & Chomont, N. The multifaceted nature of HIV latency. J. Clin. Invest. 130 , 3381–3390 (2020).

Claussnitzer, M. et al. A brief history of human disease genetics. Nature 577 , 179–189 (2020).

Naranbhai, V. & Carrington, M. Host genetic variation and HIV disease: from mapping to mechanism. Immunogenetics 69 , 489–498 (2017).

An, P. et al. Regulatory polymorphisms in the cyclophilin A gene, PPIA, accelerate progression to AIDS. PLoS Pathog. 3 , e88 (2007).

Article   PubMed   PubMed Central   CAS   Google Scholar  

Bashirova, A. A. et al. Consistent effects of TSG101 genetic variability on multiple outcomes of exposure to human immunodeficiency virus type 1. J. Virol. 80 , 6757–6763 (2006).

Boniotto, M. et al. Polymorphisms in the MBL2 promoter correlated with risk of HIV-1 vertical transmission and AIDS progression. Genes Immun. 1 , 346–348 (2000).

Bochud, P.-Y. et al. Polymorphisms in Toll-like receptor 9 influence the clinical course of HIV-1 infection. AIDS 21 , 441–446 (2007).

An, P. et al. APOBEC3G genetic variants and their influence on the progression to AIDS. J. Virol. 78 , 11070–11076 (2004).

Javanbakht, H. et al. Effects of human TRIM5alpha polymorphisms on antiretroviral function and susceptibility to human immunodeficiency virus infection. Virology 354 , 15–27 (2006).

Fellay, J. et al. Common genetic variation and the control of HIV-1 in humans. PLoS Genet. 5 , e1000791 (2009).

International HIV Controllers Studyet al. The major genetic determinants of HIV-1 control affect HLA class I peptide presentation. Science 330 , 1551–1557 (2010).

Article   CAS   Google Scholar  

McLaren, P. J. et al. Association study of common genetic variants and HIV-1 acquisition in 6,300 infected cases and 7,200 controls. PLoS Pathog. 9 , e1003515 (2013). This GWAS of HIV-1 acquisition showed no evidence for association outside of CCR5 including lack of replication of 22 loci previously claimed to impact acquisition .

Dean, M. et al. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE. Science 273 , 1856–1862 (1996). We believe this study to be the first description of host genetic resistance to an infectious disease observed in people homozygous for a loss of function mutation in CCR5 (previously known as CKR5 ) .

Huang, Y. et al. The role of a mutant CCR5 allele in HIV-1 transmission and disease progression. Nat. Med. 2 , 1240–1243 (1996).

Liu, R. et al. Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell 86 , 367–377 (1996).

Kaslow, R. A. et al. Influence of combinations of human major histocompatibility complex genes on the course of HIV-1 infection. Nat. Med. 2 , 405–411 (1996).

Tam, V. et al. Benefits and limitations of genome-wide association studies. Nat. Rev. Genet. 20 , 467–484 (2019).

Das, S., Abecasis, G. R. & Browning, B. L. Genotype imputation from large reference panels. Annu. Rev. Genomics Hum. Genet. 19 , 73–96 (2018).

Fellay, J. et al. A whole-genome association study of major determinants for host control of HIV-1. Science 317 , 944–947 (2007). In what is considered to be the first GWAS of an infectious disease phenotype, the authors demonstrate the large impact of genetic variation in the HLA region on determining HIV spVL.

Mellors, J. W. et al. Quantitation of HIV-1 RNA in plasma predicts outcome after seroconversion. Ann. Intern. Med. 122 , 573–579 (1995).

Quinn, T. C. et al. Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group. N. Engl. J. Med. 342 , 921–929 (2000).

Pelak, K. et al. Host determinants of HIV-1 control in African Americans. J. Infect. Dis. 201 , 1141–1149 (2010).

Lingappa, J. R. et al. Genomewide association study for determinants of HIV-1 acquisition and viral set point in HIV-1 serodiscordant couples with quantified virus exposure. PLoS ONE 6 , e28632 (2011).

Luo, M. et al. A genetic polymorphism of FREM1 is associated with resistance against HIV infection in the Pumwani Sex Worker Cohort. J. Virol. 86 , 11899–11905 (2012).

Mclaren, P. J. et al. Fine-mapping classical HLA variation associated with durable host control of HIV-1 infection in African Americans. Hum. Mol. Genet. 21 , 4334–4347 (2012).

Khera, A. V. et al. Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nat. Genet. 50 , 1219–1224 (2018).

McLaren, P. J. et al. Evaluating the impact of functional genetic variation on HIV-1 control. J. Infect. Dis. 216 , 1063–1069 (2017).

Lane, J. et al. A genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A. Hum. Mol. Genet. 22 , 1903–1910 (2013).

Mackelprang, R. D. et al. Whole genome sequencing of extreme phenotypes identifies variants in CD101 and UBE2V1 associated with increased risk of sexually acquired HIV-1. PLoS Pathog. 13 , e1006703 (2017).

Bouloc, A., Bagot, M., Delaire, S., Bensussan, A. & Boumsell, L. Triggering CD101 molecule on human cutaneous dendritic cells inhibits T cell proliferation via IL-10 production. Eur. J. Immunol. 30 , 3132–3139 (2000).

Xia, Z.-P. et al. Direct activation of protein kinases by unanchored polyubiquitin chains. Nature 461 , 114–119 (2009).

Pertel, T. et al. TRIM5 is an innate immune sensor for the retrovirus capsid lattice. Nature 472 , 361–365 (2011).

Powell, T. R. et al. The behavioral, cellular and immune mediators of HIV-1 acquisition: new insights from population genetics. Sci. Rep. 10 , 3304 (2020).

Petrovski, S. et al. Common human genetic variants and HIV-1 susceptibility: a genome-wide survey in a homogeneous African population. AIDS 25 , 513–518 (2011).

Shiina, T., Hosomichi, K., Inoko, H. & Kulski, J. K. The HLA genomic loci map: expression, interaction, diversity and disease. J. Hum. Genet. 54 , 15–39 (2009).

Horton, R. et al. Gene map of the extended human MHC. Nat. Rev. Genet. 5 , 889–899 (2004).

de Bakker, P. I. W. & Raychaudhuri, S. Interrogating the major histocompatibility complex with high-throughput genomics. Hum. Mol. Genet. 21 , 1–8 (2012).

Kennedy, A. E., Ozbek, U. & Dorak, M. T. What has GWAS done for HLA and disease associations? Int. J. Immunogenet. 44 , 195–211 (2017).

Venkataraman, G. R. et al. Pervasive additive and non-additive effects within the HLA region contribute to disease risk in the UK Biobank. Preprint at bioRxiv https://doi.org/10.1101/2020.05.28.119669 (2020).

Article   Google Scholar  

Sakaue, S. et al. A global atlas of genetic associations of 220 deep phenotypes. Preprint at medRxiv https://doi.org/10.1101/2020.10.23.20213652 (2020).

Carrington, M. et al. HLA and HIV-1: heterozygote advantage and B*35-Cw*04 disadvantage. Science 283 , 1748–1752 (1999).

Migueles, S. A. et al. HLA B*5701 is highly associated with restriction of virus replication in a subgroup of HIV-infected long term nonprogressors. Proc. Natl Acad. Sci. USA 97 , 2709–2714 (2000).

Gao, X. et al. Effect of a single amino acid change in MHC class I molecules on the rate of progression to AIDS. N. Engl. J. Med. 344 , 1668–1675 (2001).

Kiepiela, P. et al. Dominant influence of HLA-B in mediating the potential co-evolution of HIV and HLA. Nature 432 , 769–775 (2004).

Jia, X. et al. Imputing amino acid polymorphisms in human leukocyte antigens. PLoS ONE 8 , e64683 (2013).

McLaren, P. J. et al. Polymorphisms of large effect explain the majority of the host genetic contribution to variation of HIV-1 virus load. Proc. Natl Acad. Sci. USA 112 , 14658–14663 (2015).

Luo, Y. et al. A high-resolution HLA reference panel capturing global population diversity enables multi-ethnic fine-mapping in HIV host response. Preprint at medRxiv https://doi.org/10.1101/2020.07.16.20155606 (2020). This paper presents a framework for HLA allele imputation and association testing from genome-wide SNP data and presents a detailed fine-mapping of HLA functional variation in ~12,000 PLWH.

Article   PubMed   PubMed Central   Google Scholar  

Kelleher, A. D. et al. Clustered mutations in HIV-1 gag are consistently required for escape from Hla-B27–restricted cytotoxic T lymphocyte responses. J. Exp. Med. 193 , 375–386 (2001).

Martinez-Picado, J. et al. Fitness cost of escape mutations in p24 Gag in association with control of human immunodeficiency virus type 1. J. Virol. 80 , 3617–3623 (2006).

Schneidewind, A. et al. Escape from the dominant HLA-B27-restricted cytotoxic T-lymphocyte response in Gag is associated with a dramatic reduction in human immunodeficiency virus type 1 replication. J. Virol. 81 , 12382–12393 (2007).

Migueles, S. A. et al. HIV-specific CD8 + T cell proliferation is coupled to perforin expression and is maintained in nonprogressors. Nat. Immunol. 3 , 1061–1068 (2002).

Horton, H. et al. Preservation of T cell proliferation restricted by protective HLA alleles is critical for immune control of HIV-1 infection. J. Immunol. 177 , 7406–7415 (2006).

Almeida, J. R. et al. Superior control of HIV-1 replication by CD8 + T cells is reflected by their avidity, polyfunctionality, and clonal turnover. J. Exp. Med. 204 , 2473–2485 (2007).

Arora, J. et al. HLA heterozygote advantage against HIV-1 is driven by quantitative and qualitative differences in HLA allele-specific peptide presentation. Mol. Biol. Evol. 37 , 639–650 (2020).

Arora, J. et al. HIV peptidome-wide association study reveals patient-specific epitope repertoires associated with HIV control. Proc. Natl Acad. Sci. USA 116 , 944–949 (2019).

Gaiha, G. D. et al. Structural topology defines protective CD8 + T cell epitopes in the HIV proteome. Science 364 , 480–484 (2019). Using network analysis to quantify the structural importance of amino acids in HIV proteins, the authors show that mutations in epitopes presented by protective HLA class I alleles disproportionately impair viral replication.

Apps, R. et al. Influence of HLA-C expression level on HIV control. Science 340 , 87–91 (2013). This paper demonstrates that HLA-C expression level rather than epitope presentation is the key mediator of its impact on host control of HIV replication.

Kulkarni, S. et al. Differential microRNA regulation of HLA-C expression and its association with HIV control. Nature 472 , 495–498 (2011).

Ramsuran, V. et al. Epigenetic regulation of differential HLA-A allelic expression levels. Hum. Mol. Genet. 24 , 4268–4275 (2015).

Ramsuran, V. et al. Elevated HLA-A expression impairs HIV control through inhibition of NKG2A-expressing cells. Science 359 , 86–90 (2018). Furthering work on non-classical HLA effects in HIV control, this paper demonstrates how the expression level of the HLA-A signal peptide can regulate the HLA-E–NKG2A interaction modulating spVL.

Martin, M. P. & Carrington, M. Immunogenetics of HIV disease. Immunol. Rev. 254 , 245–264 (2013).

Pende, D. et al. Killer Ig-like receptors (KIRs): their role in NK cell modulation and developments leading to their clinical exploitation. Front. Immunol. 10 , 1179 (2019).

Martin, M. P. et al. Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS. Nat. Genet. 31 , 429–434 (2002).

Novembre, J., Galvani, A. P. & Slatkin, M. The geographic spread of the CCR5 Δ32 HIV-resistance allele. PLoS Biol. 3 , 1954–1962 (2005).

Hladik, F. et al. Combined effect of CCR5-Delta32 heterozygosity and the CCR5 promoter polymorphism -2459 A/G on CCR5 expression and resistance to human immunodeficiency virus type 1 transmission. J. Virol. 79 , 11677–11684 (2005).

Fätkenheuer, G. et al. Efficacy of short-term monotherapy with maraviroc, a new CCR5 antagonist, in patients infected with HIV-1. Nat. Med. 11 , 1170–1172 (2005).

Article   PubMed   CAS   Google Scholar  

Wang, H. & Yang, H. Gene-edited babies: what went wrong and what could go wrong. PLoS Biol. 17 , e3000224 (2019).

Hutter, G. et al. Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. N. Engl. J. Med. 360 , 692–698 (2009). This is the first description of a functional cure of HIV infection in a patient who received a stem cell transplant from a donor homozygous for the CCR5Δ32 polymorphism .

Gupta, R. K. et al. Evidence for HIV-1 cure after CCR5Δ32/Δ32 allogeneic haemopoietic stem-cell transplantation 30 months post analytical treatment interruption: a case report. Lancet HIV 7 , e340–e347 (2020).

Tebas, P. et al. Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV. N. Engl. J. Med. 370 , 901–910 (2014).

Smoleń-Dzirba, J. et al. HIV-1 infection in persons homozygous for CCR5-Δ32 allele: the next case and the review. AIDS Rev. 19 , 219–230 (2017).

Michael, N. L. et al. The role of viral phenotype and CCR-5 gene defects in HIV-1 transmission and disease progression. Nat. Med. 3 , 338–340 (1997).

Kulkarni, S. et al. CCR5AS lncRNA variation differentially regulates CCR5, influencing HIV disease outcome. Nat. Immunol. 20 , 824–834 (2019).

Carlson, J. M., Le, A. Q., Shahid, A. & Brumme, Z. L. HIV-1 adaptation to HLA: a window into virus-host immune interactions. Trends Microbiol. 23 , 212–224 (2015).

Alter, G. et al. HIV-1 adaptation to NK-cell-mediated immune pressure. Nature 476 , 96–100 (2011).

Hölzemer, A. et al. Selection of an HLA-C*03:04-Restricted HIV-1 p24 Gag sequence variant is associated with viral escape from KIR2DL3+ natural killer cells: data from an observational cohort in South Africa. PLoS Med. 12 , e1001900 (2015).

Snoeck, J., Fellay, J., Bartha, I., Douek, D. C. & Telenti, A. Mapping of positive selection sites in the HIV-1 genome in the context of RNA and protein structural constraints. Retrovirology 8 , 87 (2011).

Bartha, I. et al. A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control. eLife 2 , e01123 (2013). This paper proposes the G2G method and demonstrates that viral genetic variation can be a more powerful phenotype than clinical markers for host–pathogen genomic studies.

Palmer, D. S. et al. Mapping the drivers of within-host pathogen evolution using massive data sets. Nat. Commun. 10 , 3017 (2019).

Fellay, J. & Pedergnana, V. Exploring the interactions between the human and viral genomes. Hum. Genet. 139 , 777–781 (2020).

Ansari, M. A. et al. Genome-to-genome analysis highlights the effect of the human innate and adaptive immune systems on the hepatitis C virus. Nat. Genet. 49 , 666–673 (2017). Applying the G2G approach to hepatitis C virus, the authors demonstrate that it can be used to detect viral evolution owing to both innate and adaptive host immune pressure.

Chaturvedi, N. et al. Adaptation of hepatitis C virus to interferon lambda polymorphism across multiple viral genotypes. eLife 8 , e42542 (2019).

Rüeger, S. et al. The influence of human genetic variation on Epstein-Barr virus sequence diversity. Sci. Rep. 11 , 4586 (2021).

Eisinger, R. W., Dieffenbach, C. W. & Fauci, A. S. HIV viral load and transmissibility of HIV infection: undetectable equals untransmittable. JAMA 321 , 451–452 (2019).

Joint United Nations Programme on HIV/AIDS. 90–90–90: an ambitious treatment target to help end the AIDS epidemic (UNAIDS, 2014).

Lubomirov, R. et al. Association of pharmacogenetic markers with premature discontinuation of first-line anti-HIV therapy: an observational cohort study. J. Infect. Dis. 203 , 246–257 (2011).

Mallal, S. et al. Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir. Lancet 359 , 727–732 (2002).

Hetherington, S. et al. Genetic variations in HLA-B region and hypersensitivity reactions to abacavir. Lancet 359 , 1121–1122 (2002).

Norcross, M. A. et al. Abacavir induces loading of novel self-peptides into HLA-B*57: 01: an autoimmune model for HLA-associated drug hypersensitivity. AIDS 26 , F21–F29 (2012).

Rotger, M. et al. Predictive value of known and novel alleles of CYP2B6 for efavirenz plasma concentrations in HIV-infected individuals. Clin. Pharmacol. Ther. 81 , 557–566 (2007).

Arab-Alameddine, M. et al. Pharmacogenetics-based population pharmacokinetic analysis of efavirenz in HIV-1-infected individuals. Clin. Pharmacol. Ther. 85 , 485–494 (2009).

Haas, D. W. et al. Pharmacogenetics of efavirenz and central nervous system side effects: an Adult AIDS Clinical Trials Group study. AIDS 18 , 2391–2400 (2004).

CAS   PubMed   Google Scholar  

di Iulio, J. et al. In vivo analysis of efavirenz metabolism in individuals with impaired CYP2A6 function. Pharmacogenet. Genomics 19 , 300–309 (2009).

Lubomirov, R. et al. Pharmacogenetics-based population pharmacokinetic analysis of etravirine in HIV-1 infected individuals. Pharmacogenet. Genomics 23 , 9–18 (2013).

Lubomirov, R. et al. ADME pharmacogenetics: investigation of the pharmacokinetics of the antiretroviral agent lopinavir coformulated with ritonavir. Pharmacogenet. Genomics 20 , 217–230 (2010).

Zanger, U. M. & Klein, K. Pharmacogenetics of cytochrome P450 2B6 (CYP2B6): advances on polymorphisms, mechanisms, and clinical relevance. Front. Genet. 4 , 24 (2013).

Nordling, L. How the genomics revolution could finally help Africa. Nature 544 , 20–22 (2017).

Kanters, S. et al. Comparative efficacy and safety of first-line antiretroviral therapy for the treatment of HIV infection: a systematic review and network meta-analysis. Lancet HIV 3 , e510–e520 (2016).

Currier, J. S. et al. Coronary heart disease in HIV-infected individuals. J. Acquir. Immune Defic. Syndr. 33 , 506–512 (2003).

Obel, N. et al. Ischemic heart disease in HIV-infected and HIV-uninfected individuals: a population-based cohort study. Clin. Infect. Dis. 44 , 1625–1631 (2007).

Lang, S. et al. Increased risk of myocardial infarction in HIV-infected patients in France, relative to the general population. AIDS 24 , 1228–1230 (2010).

Périard, D. et al. Atherogenic dyslipidemia in HIV-infected individuals treated with protease inhibitors. The Swiss HIV cohort study. Circulation 100 , 700–705 (1999).

Nadkarni, G. N. et al. The burden of dialysis-requiring acute kidney injury among hospitalized adults with HIV infection: a nationwide inpatient sample analysis. AIDS 29 , 1061–1066 (2015).

Scherzer, R. et al. Association of tenofovir exposure with kidney disease risk in HIV infection. AIDS 26 , 867–875 (2012).

Li, Y. et al. Combination antiretroviral therapy is associated with reduction in liver fibrosis scores in HIV-1-infected subjects. Medicine 95 , e2660 (2016).

Rotger, M. et al. Impact of single nucleotide polymorphisms and of clinical risk factors on new-onset diabetes mellitus in HIV-infected individuals. Clin. Infect. Dis. 51 , 1090–1098 (2010).

Rotger, M. et al. Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons. Clin. Infect. Dis. 57 , 112–121 (2013).

Dietrich, L. G. et al. Contribution of genetic background and data collection on adverse events of anti-human immunodeficiency virus (HIV) drugs (D:A:D) clinical risk score to chronic kidney disease in Swiss HIV-infected persons with normal baseline estimated glomerular filtration rate. Clin. Infect. Dis. 70 , 890–897 (2020).

Dietrich, L. G. et al. Rapid progression of kidney dysfunction in swiss people living with HIV: contribution of polygenic risk score and D:A:D clinical risk score. J. Infect. Dis. 223 , 2145–2153 (2021).

Chang, H. et al. Genetic architecture of cardiometabolic risks in people living with HIV. BMC Med. 18 , 288 (2020).

Article   CAS   PubMed Central   Google Scholar  

Popejoy, A. B. & Fullerton, S. M. Genomics is failing on diversity. Nature 538 , 161–164 (2016).

Rotman, D. DNA databases are too white: this man aims to fix that. MIT Technol. Rev. http://www.technologyreview.com/2018/10/15/139472/dna-databases-are-too-white-this-man-aims-to-fix-that/ (2018).

Vukcevic, D. et al. Imputation of KIR types from SNP variation data. Am. J. Hum. Genet. 97 , 593–607 (2015).

Kawaguchi, S., Higasa, K., Shimizu, M., Yamada, R. & Matsuda, F. HLA-HD: an accurate HLA typing algorithm for next-generation sequencing data. Hum. Mutat. 38 , 788–797 (2017).

Kim, D., Paggi, J. M., Park, C., Bennett, C. & Salzberg, S. L. Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype. Nat. Biotechnol. 37 , 907–915 (2019).

Roe, D. & Kuang, R. Accurate and efficient KIR gene and haplotype inference from genome sequencing reads with novel K-mer signatures. Front. Immunol. 11 , 583013 (2020).

Sarkar, I., Hauber, I., Hauber, J. & Buchholz, F. HIV-1 proviral DNA excision using an evolved recombinase. Science 316 , 1912–1915 (2007).

Hu, W. et al. RNA-directed gene editing specifically eradicates latent and prevents new HIV-1 infection. Proc. Natl Acad. Sci. USA 111 , 11461–11466 (2014).

Ge, D. et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 461 , 399–401 (2009).

Thomas, D. L. et al. Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature 461 , 798–801 (2009).

Thye, T. et al. Genome-wide association analyses identifies a susceptibility locus for tuberculosis on chromosome 18q11.2. Nat. Genet. 42 , 739–741 (2010).

Malaria Genomic Epidemiology Network. A novel locus of resistance to severe malaria in a region of ancient balancing selection. Nature 526 , 253–257 (2015).

Article   PubMed Central   CAS   Google Scholar  

Zhang, Q. et al. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science 370 , eabd4570 (2020).

Sul, J. H., Martin, L. S. & Eskin, E. Population structure in genetic studies: confounding factors and mixed models. PLoS Genet. 14 , e1007309 (2018).

Download references

Author information

Authors and affiliations.

National HIV and Retrovirology Laboratory at the JC Wilt Infectious Diseases Research Centre, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada

• Paul J. McLaren

Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada

School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

• Jacques Fellay

Swiss Institute of Bioinformatics, Lausanne, Switzerland

Precision Medicine Unit, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

You can also search for this author in PubMed   Google Scholar

Contributions

The authors contributed equally to all aspects of the article.

Corresponding author

Correspondence to Jacques Fellay .

Ethics declarations

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.

HIV is the causative agent of AIDS, which is a state of severe immune deficiency defined as an HIV infection with either a CD4 + T cell count <200 cells/µl or the occurrence of a specific AIDS-defining illness.

(CCR5). A β-chemokine receptor that is involved in lymphocyte trafficking. In combination with CD4, CCR5 is the major host cell receptor for HIV and interacts with gp120 in the viral envelope to promote cell entry and infection.

(CTLs). Cytotoxic T cells (also called CD8 + T cells) are effector T lymphocytes that specifically kill target cells that express an appropriate peptide–MHC class I complex recognised by its T cell receptor.

( HLA). A protein, encoded by one of a group of HLA genes, that presents antigens that train the adaptive immune response. HLA genes are highly variable and allelic variants encode proteins that are differentially able to present antigens based on the amino acid sequences in the peptide-binding grooves.

Parts of an antigen that make contact with a particular antibody or T cell receptor and are thus capable of stimulating an immune response.

(PRS). Statistics that are calculated by enumerating the number of risk alleles associated with a particular phenotype (often weighted by their population-level effect sizes) that are present in a single individual and comparing the individual’s score to the distribution of risk scores in the population.

Presence of systematic differences in allele frequencies between population subgroups owing to systematic differences in ancestry.

The natural disease course of HIV infection in untreated individuals, characterized by an acute phase, a chronic phase and the development of AIDS. The rate of HIV progression varies dramatically in the infected population.

The long-term persistence of HIV in an integrated but transcriptionally inactive form in the host genome. Because latent HIV resides in memory T cells, it persists indefinitely even in patients on suppressive antiretroviral therapy. This latent reservoir is a major barrier to curing HIV infection.

(spVL). Mean log viral load (HIV RNA copies per millilitre of plasma) measured in an individual with HIV infection during the chronic phase of infection. The spVL varies substantially within a population and correlates with disease progression.

Underlying genetic basis of a given trait, in terms of variant number, effect size, allele frequency and interactions.

A group of people living with HIV whose plasma HIV RNA load is spontaneously maintained at very low levels for several years (usually at least 3–5 years) in the absence of antiretroviral therapy.

A host cellular protein that participates in antiviral defence by interfering with specific steps of the viral replication cycle.

( KIR). A family of highly polymorphic activating and inhibitory receptors that serve as key regulators of human natural killer cell function.

The cells primarily infected by HIV, namely CD4 + T cells and macrophages, both of which are key components of a healthy immune system.

A mechanism in which the RALY protein binds to the 3′ untranslated region of an mRNA to promote its degradation.

The single viral variant that is responsible for a new infection after being transferred from an infected individual to an uninfected individual. Sexually transmitted HIV infections are typically established from a single transmitted/founder virus.

Methods that test the hypothesis that host genetic variability causes pathogen genetic variability and can indicate novel host restriction factors.

Strategy to prevent the sexual transmission of HIV through the prescription of HIV medication. It is a highly effective option for preventing HIV transmission. People living with HIV who take antiretroviral drugs and maintain an undetectable viral load have effectively no risk of sexually transmitting the virus to their HIV-negative partners.

Rights and permissions

Reprints and permissions

About this article

Cite this article.

McLaren, P.J., Fellay, J. HIV-1 and human genetic variation. Nat Rev Genet 22 , 645–657 (2021). https://doi.org/10.1038/s41576-021-00378-0

Download citation

Accepted : 11 May 2021

Published : 24 June 2021

Issue Date : October 2021

DOI : https://doi.org/10.1038/s41576-021-00378-0

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

This article is cited by

Comparison of pharmacokinetics and safety of albuvirtide in healthy subjects after intravenous drip and bolus injection.

• Huiling Qin

Naunyn-Schmiedeberg's Archives of Pharmacology (2024)

The metabolic consequences of HIV/TB co-infection

• Chandré Herbert
• Laneke Luies
• Aurelia A. Williams

BMC Infectious Diseases (2023)

Variation in African genomes linked to control of HIV

Nature (2023)

Africa-specific human genetic variation near CHD1L associates with HIV-1 load

• Immacolata Porreca

Quick links

• Explore articles by subject
• Guide to authors
• Editorial policies

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

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

Trends and emerging directions in HIV risk and prevention research in the Philippines: A systematic review of the literature

Contributed equally to this work with: Arjee Restar, Mary Nguyen

Roles Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing

* E-mail: [email protected]

Affiliation Department of Behavioral and Social Sciences, Brown University School of Public Health, Providence, Rhode Island, United States of America

Roles Data curation, Methodology, Project administration, Software, Writing – review & editing

Roles Data curation, Methodology, Visualization, Writing – review & editing

Roles Data curation, Formal analysis, Methodology, Software, Visualization, Writing – review & editing

Roles Data curation, Formal analysis, Investigation, Writing – review & editing

Affiliation Department of Behavioral Sciences, University of the Philippines, Manila, Philippines

• Arjee Restar, 
• Mary Nguyen, 
• Kimberly Nguyen, 
• Alexander Adia, 
• Jennifer Nazareno, 
• Emily Yoshioka, 
• Laufred Hernandez, 
• Don Operario

• Published: December 5, 2018
• https://doi.org/10.1371/journal.pone.0207663
• Reader Comments

The Philippines is experiencing one of the fastest growing epidemics globally. Evidence-based public health policies are needed. To describe the public health literature on HIV risk groups and prevention approaches in the Philippines, we reviewed published empirical studies with HIV-related outcomes.

Based on an a priori systematic review protocol, we searched PubMed, PsycINFO and CINAHL databases for quantitative studies conducted in the Philippines that reported on HIV risk groups factors and interventions to prevent HIV. The search included studies published as of April 2018.

We identified 755 records, screened 699 unique titles and abstracts, and conducted full text review of 122 full reports of which 51 articles met inclusion criteria. The majority were cross-sectional studies describing HIV and STI prevalence and risk factors in samples recruited from the Philippines. Four HIV prevention programs conducted in the Philippines were identified, all of which reported improvements on HIV knowledge, attitudes, and behaviors. Overall, female sex workers (FSWs) constituted the primary study population, and few studies reported data from men who have sex with men (MSM), people who inject drugs (PWIDs), and youth. No studies reported on transgender populations. Most studies were focused on examining condom use-related outcomes and STI history, few had biomarkers for HIV, and none addressed biomedical HIV prevention strategies.

This review identifies an agenda for future HIV research that is needed to address the growing and shifting nature of the HIV epidemic in the Philippines.

Citation: Restar A, Nguyen M, Nguyen K, Adia A, Nazareno J, Yoshioka E, et al. (2018) Trends and emerging directions in HIV risk and prevention research in the Philippines: A systematic review of the literature. PLoS ONE 13(12): e0207663. https://doi.org/10.1371/journal.pone.0207663

Editor: Jerome T. Galea, University of South Florida, UNITED STATES

Received: July 16, 2018; Accepted: November 5, 2018; Published: December 5, 2018

Copyright: © 2018 Restar 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 can be found in Table 1 of the paper and our search strategy is detailed in our methods section.

Funding: Study was supported by National Institutes of Health(NIH)-Fogarty D43TW010565, NIH-NIAID P30AI042853, Brown University Global Health Scholars program, and the Robert Wood Johnson Foundation (RWJF) Health Policy Research Scholars program (awarded to Arjee Restar). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, Brown University, nor RWJF.

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

Introduction

After the first HIV case was identified in the Philippines in 1984, the country’s estimated HIV prevalence had remained low for over two decades [ 1 ]. According to the Joint United Nations Programme on HIV/AIDS (UNAIDS)’s surveillance reports, the Philippines’ progress towards reaching HIV/AIDS 90-90-90 treatment for people living with HIV and knowing their HIV status (67%), on treatment (32%), and are virally suppressed (29%), is slow as HIV infections rise in the Philippines [ 2 ]. National surveillance data showed that the number of new HIV cases in the Philippines started to rise at an alarming rate during the past decade, with an increase from 311 cases identified in 2007 to 8,151 cases identified in 2016 –representing a 26-fold increase in new HIV diagnoses [ 3 ]. According to a 2014 national report, 93% of HIV cases in the Philippines were transmitted through sexual contact and were particularly concentrated among youth and young adults [ 4 ].

Despite the growing HIV epidemic in the Philippines, there have been challenges in mobilizing local and national HIV prevention, education, and testing programs [ 5 , 6 ]. Evidence-based public health is needed. However, a 2015 report by the World Health Organization (WHO) highlights that the body of HIV research conducted in the Philippines has been limited across all areas, including prevention, epidemiology, evaluation, and behavioral science, which are each essential to developing effective public health strategies [ 7 , 8 ].

Some of the recognized key populations for HIV risk in the Philippines include men who have sex with men (MSM), transgender people, female sex workers (FSW), youth, and overseas workers [ 1 , 6 , 7 ]. Although the estimated number of people who inject drugs (PWID) in the Philippines has been historically low, there have been anecdotal reports suggesting a growth in this population [ 9 ]. The National AIDS and STI Prevention and Control Program for the Philippines has urged for the development of HIV prevention and public health initiatives targeted towards key populations [ 7 ]. However, an external review by the WHO of the national response acknowledged multi-level challenges in implementing HIV prevention and treatment activities, including a misalignment of healthcare priorities in the national- and city-level settings, limited healthcare infrastructure and human resources to provide prevention and treatment services to key populations, and a nascent research literature on which to build evidence-informed strategies [ 7 ].

We conducted a systematic review to examine the body of empirical literature on HIV risk and intervention programs in the Philippines. Our specific aims were to synthesize findings about population characteristics associated with HIV status or HIV risk in the Philippines, to identify and describe local HIV prevention interventions evaluated in the Philippines, and to describe the methodological characteristics of this body of research. As a secondary aim, we sought to describe differences in reported HIV risk in studies conducted before 2008 compared with studies published during or after 2008, which represents the year during which national surveillance observed noted increased HIV cases.

We conducted this systematic review in accordance with guidelines set by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and checklist [ 10 ], which can be found in S1 Fig . Fig 1 displays the flowchart of review’s article section, inclusion and exclusion.

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

https://doi.org/10.1371/journal.pone.0207663.g001

Search strategy

We searched for quantitative studies assessing biological or behavioral indicators of HIV risk among Filipino/a participants in the Philippines. Studies were included if they: 1) were conducted in the Philippines; 2) sampled Filipino/a participants; 3) published in English; 4) reported quantitative findings on any of the following category of outcomes: biological risk for HIV (biomarkers/biologically confirmed HIV or other STIs); self-reported HIV status or STI diagnoses or symptoms; HIV-related sexual risk behavior (such as condomless sex, commercial sex, sex under influence of drugs/alcohol, sex with partner of HIV-positive or unknown status); injection drug use; knowledge, attitudes and beliefs relating to HIV/AIDS risk and transmission. We did not limit studies according to type of quantitative design (i.e., cross-sectional, intervention trial, etc.) or presence of a comparison or control group.

Electronic searches of PubMed, PsycINFO, and CINAHL were carried out using an a priori search strategy in April 2018. The search strategy included validated MeSH terms for HIV as well as terms related to Philippines. For example, the PubMed search used the following terms: [HIV* OR AIDS* OR HIV Infections[MeSH] OR HIV[MeSH] OR hiv[tw] OR hiv-1*[tw] OR hiv-2*[tw] OR hiv1[tw] OR hiv2[tw] OR hiv infect*[tw] OR human immunodeficiency virus[tw] OR human immunodeficiency virus[tw] OR human immuno-deficiency virus[tw] OR human immune-deficiency virus[tw] OR ((human immuno*) AND (deficiency virus[tw])) OR acquired immunodeficiency syndrome[tw] OR acquired immunodeficiency syndrome[tw] OR acquired immuno-deficiency syndrome[tw] OR acquired immune-deficiency syndrome[tw] OR ((acquired immuno*) AND (deficiency syndrome[tw])) OR “Sexually Transmitted Diseases, Viral”[MeSH:NoExp]] and Philippines. The search strings were intended to be conservative to first capture articles that relevant to the scope of the study and then identify articles meeting inclusion criteria.

This search yielded 755 records (see Fig 1 for a flowchart of the systematic review process). A team of reviewers received training in applying the inclusion criteria to research records; reviewers applied the screening criteria to an initial batch of 100 records and discussed discrepancies until reliability was achieved. Screeners were instructed to apply initial inclusion criteria liberally, such that records were retained in the search process until the team was sure that studies did not meet inclusion criteria. After excluding 56 duplicate records from the database, two reviewers screened the remaining 699 records resulting in a shortlist of 122 records that appeared to meet inclusion criteria based on information in the title or abstract. These articles were retrieved for full text review, which was performed by four reviewers (including the 2 previous reviewers) who identified 51 articles that met inclusion criteria. We excluded 71 articles because they were not based in the Philippines, were not empirical studies (i.e. editorials, commentaries, or reviews), or did not report on outcomes specified for this review. We identified several articles meeting inclusion criteria that reported different findings from the same parent research study; these articles were retained in this review.

Data extraction and analysis

The overarching goal of this review was to summarize trends in the published literature and appraise the methodological quality of identified studies. For all research articles that met inclusion criteria, we extracted information about the year(s) of data collection, study sample and location, sampling method, study design, HIV-related outcome(s), and main findings (see Table 1 ). Articles that reported data from the same parent study are grouped together in Table 1 , with the primary or lead article denoted by superscript “a” and subsequent articles denoted by “b”, “c”, etc.

https://doi.org/10.1371/journal.pone.0207663.t001

Narrative synthesis of studies was conducted based on information extracted into Table 1 . Because of heterogeneity in sampling approaches, time, and indicators of HIV risk across studies, meta-analysis was not conducted. We assessed methodological characteristics of each study using a critical appraisal checklist developed by Munn and colleagues [ 11 ]. These methodological characteristics included sample representativeness, recruitment strategies, adequacy of sample size, participant drop-out or non-response, description of setting and participant, objective criteria for outcome measurements, reliability of outcome, appropriateness of statistical analysis, accounting of confounding factors, and identification of sub-populations.

Authors were not blind to any aspect of the studies. Funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Characteristics of included studies

Table 1 presents characteristics of 51 included articles from 30 independent studies. Twenty-five articles reported quantitative findings from independent studies [ 12 – 36 ]. Two articles reported analyses from a cross-sectional survey of sexual behaviors among adult men and women from Cebu (a large metropolitan city in the Philippines) [ 37 – 38 ]. Fifteen articles reported analyses from a longitudinal, quasi-experimental investigation of a community-based HIV prevention program involving female bar workers and managers in four regions of the Philippines [ 39 – 53 ]. Four articles reported findings from a quasi-experimental intervention to prevent HIV and STIs among heterosexuals in southern Philippines [ 54 – 57 ]. Two articles reported analyses of a survey of people who inject drugs in Manila, Cebu, and Davao cities [ 58 – 59 ]. Three articles reported analyses of a survey of FSW recruited from entertainment establishments in metro Manila [ 60 – 62 ].

Overall, data collection for the included studies occurred between years 1985 to 2015. Of 30 independent studies, most (n = 18) studies reported findings from data collected before 2008 and 10 studies reporting findings from data collected during or after 2008; 2 studies did not specify year of data collection, but both were published before 2008. Sample sizes per study ranged from 62 to 144,000; the latter study involved analysis of blood bank data. Female sex workers (e.g., registered and freelance) constituted the most frequently studied population (n = 11 unique studies). Fewer studies reported data on MSM (n = 3 unique studies), PWID (n = 3 unique studies), youth (n = 4 unique studies), seafarers (n = 3 unique studies), or incarcerated females (n = 1 study). One study reported on overseas worker candidates [ 35 ]. No included studies reported data on overseas workers and transgender populations, and no studies reported data on gender expression or gender identity indicators.

The majority of articles (n = 43) reported descriptive data from cross-sectional designs (including baseline data from intervention evaluations). Only 4 independent intervention studies were identified, with evaluation findings reported across 9 different articles [ 17 , 32 , 39 , 41 , 42 , 47 , 48 , 54 , 55 ].

Ten articles reporting data from 9 independent studies reported prevalence of HIV-positive status [ 13 , 20 , 21 , 23 , 24 , 31 , 34 , 39 , 58 , 59 ]. HIV prevalence across studies ranged from 0% (in 3 independent studies of 560 female and male adults in Cebu [ 13 ], 62 blood donor samples from Manila [ 20 ], and 100 incarcerated females in Manila [ 31 ]) to 52.0% in a sample of 457 participants in Cebu who were recruited using respondent driven sampling [ 34 ]. Of the 9 independent studies reporting HIV prevalence, 6 were conducted before 2008 (HIV prevalence ranging from 0.0% [ 12 , 20 , 31 ] to 0.2% [ 24 ]) and 3 were conducted after 2008 (HIV prevalence ranging from 3.3% [ 58 ] to 52.0% [ 34 ]).

Nineteen studies reported STI diagnosis or symptoms [ 12 , 13 , 15 , 16 , 18 , 20 , 24 , 25 , 29 , 31 , 33 , 35 , 36 , 37 , 39 , 43 , 50 , 52 , 58 ]. Of those studies, four studies included Hepatitis C [ 13 , 24 , 36 , 58 ], three included Hepatitis B and gonorrhoeae each [ 13 , 18 , 20 , 31 , 35 ], two included chlamydia [ 31 , 35 ], and one for trichomonas and HPV each [ 31 , 33 ]. Reported prevalence ranged from a low of 0.4% in a sample of overseas Filipino worker candidates and blood donors who tested positive for Hepatitis B virus or Hepatitis C virus [ 36 ], to 63.1% history of any STI in a sample of FSW from Cebu [ 12 ]. There were no clear trends in reports of STI prevalence in studies conducted before versus after 2008.

Behavioral risk factors.

Commonly reported HIV risk factors included self-reported condom use, and substance use behaviors. Of the included articles, thirty-one reported condom use behaviors. Assessment of condom use varied widely across studies, including measures of condomless sex with different partner types (e.g., with sex workers, multiple sexual partners, group sex, regular partners, and casual partners), frequency of condom use (e.g., using condoms always, consistently, inconsistently, and never), condom use according to type of intercourse (e.g., condom use during vaginal or anal sex), and condom use according to specific sexual events (e.g., condom use at first sex, and during last sexual encounter). Assessment of condom attitudes and knowledge also varied, with measurements including knowing that condoms prevent HIV/AIDS, pregnancy, and STI infections, as well as feeling that condoms reduce sexual pleasure or enjoyment, and that using condoms is against religion. Only five studies reported substance use outcome measures [ 21 , 34 , 38 , 57 , 62 ], and these studies varied with regard to assessment about type, frequency, and amount of substance use.

Intervention programs.

We identified a total of four independent intervention studies aiming to prevent HIV transmission, with evaluation results reported across 9 reports [ 17 , 32 , 39 , 41 , 42 , 47 , 48 , 54 , 55 ]. One intervention study conducted in 1995 by Aplasca et al. [ 17 ] involved a cluster-randomized trial of a school-based program to improve HIV-related knowledge, attitudes, and behaviors among high school students in Manila. Findings included improved levels of knowledge about HIV biology, transmission and prevention, as well as improved attitudes and compassion for people living with HIV in the intervention versus control groups; no effects were found on intentions to engage in preventative behaviors [ 17 ]. Another intervention study conducted in 2013 by Urada et al. [ 32 ] involved a human-rights focused HIV intervention for sex workers in Manila. Participants completed a single 4-hour intervention providing HIV and STI knowledge and prevention strategies, and contextualized risk and protective factors in accordance with the laws, systems, and social milieu regarding sex work, violence, and discrimination. In pre-post analysis, participants reported higher levels of knowledge about HIV reproductive health, human rights, research ethics, and intentions to receive an HIV test [ 32 ].

Two intervention programs were quasi-experimental studies. First, a 3-year study conducted from 1994–1998 by Morisky et al. [ 39 ] used community-based participatory methods to train managers and peer educators on HIV and STI prevention at 130 entertainment establishments in 4 regions in the Philippines. Trained managers and peers then implemented and disseminated information within their establishments. In post-test evaluation analyses, FSW employed in these establishments reported significant improvements in consistent condom use, improvements in HIV testing, and reductions in STI infections [ 39 , 42 , 47 , 48 ]. Additional analyses showed that improvements in condom use were strongest in establishments that also instituted condom use policies for employees and patrons [ 41 ]. Second, a 3-year quasi-experimental study conducted from 2000–2005 by Morisky et al. [ 54 ] used community-based participatory methods to provide HIV prevention education training to peer leaders recruited from six male populations in the southern Philippines: military members, police and firemen, construction workers, taxi drivers, pedicab drivers, and community residents; trainees were then expected to educate 10 or more peer network members on HIV and STI prevention. In post-test evaluation analyses, intervention participants reported lower levels of STI infections as well as improvements in HIV and STI knowledge, attitudes toward condoms, condom use behavior, discussion about HIV with co-workers, and exposure to HIV prevention education, compared with those in the control [ 54 , 55 ].

Finally, another prospective STI treatment study was identified, but was not considered a scalable HIV prevention intervention compared with the four studies described here. In this STI treatment study conducted in 1996–1997 by Aplasca de los Reyes et al. [ 18 ], FSWs from Manila and Cebu testing positive for N . gonorrhoeae were randomly assigned to receive a single dose of ciprofloxacin (500 mg) or a single dose of cefixime (400 mg), and were re-evaluated 4–7 days later. Findings showed high rates of treatment failure and resistance in participants who received ciprofloxacin and adequate effects for single-dose cefixime [ 18 ].

Methodological appraisal of the included studies.

For selecting participants, most of the study participants were recruited using sampling methods based on non-randomized sampling strategies, including convenience and purposive sampling such as venue-based (e.g., community or establishment) recruitment approaches or from surveillance studies. Common examples of venue-based recruitments were via bars, nightclubs, karaoke TV lounges, massage parlors, and health clinics. One study reported data from a nationally representative youth survey [ 19 ], and two studies reported data from respondent driving sampling surveys [ 34 , 58 ]. Although all studies indicated the type of recruitment strategy used (e.g., convenience sampling, etc.), almost 13 did not specifically detail about how participants were recruited. All studies had adequate sample size to perform analysis, and had high participant response rate. Most studies (n = 26) provided adequate description of their participant samples and the study settings.

When considering outcomes, nineteen studies did not use objective standard criteria for measuring outcomes (i.e., validity) such as a biologically-confirmed results. Self-reported outcomes were primarily assessed and there were noticeable inconsistent measurements in condom use and substance use behavioral measures and HIV-related knowledge and attitude measures. Statistical analyses for each study were conducted appropriately based on study design. Of the four intervention studies, one used a cluster randomized control trial design, two used non-randomized comparison groups, and one used a pre-post evaluation design. Intervention studies assessed self-report behavioral outcomes only; none measured biological or objective indictors of HIV risk.

Despite the rise in HIV infections documented in the Philippines’ national surveillance reports since 2008, this review highlights the limited body of published research on HIV infection and risk factors in key populations, a paucity of research on interventions to promote HIV prevention and testing in the Philippines, and opportunities for improving methodological rigor in future research. Overall, we identified 51 published quantitative papers reporting on HIV- or STI-related biological, behavioral, or social-cognitive findings from 30 unique studies conducted in the Philippines. The majority of papers identified in this review reported on data collected before 2008; only 10 papers (reporting on 7 discrete studies) reported data collected during or after 2008. Moreover, this review identified only 4 HIV prevention intervention evaluations in the published literature.

Prior to 2008, FSWs constituted the population most frequently studied in HIV research conducted in the Philippines. After 2008, a small number of studies included MSM and PWID. Indeed, the papers by Gangcuangco and colleagues [ 21 ] and Telan and colleagues [ 59 , 60 ] and are among the only identified published studies which recruited and reported specifically on HIV risk in MSM populations. Findings from PWID were included in four reports–one involving surveillance data from an earlier phase of the epidemic [ 16 ], three conducted after 2008 by Verdery and colleagues [ 34 ] and by Telan and colleagues [ 58 , 59 ]. Four studies included youth; two were conducted before 2008 [ 17 , 19 ] and two after [ 28 , 38 ]. No identified studies specifically reported on overseas workers and transgender populations.

This review identifies a need to improve the body of knowledge about HIV risk and transmission among key populations in the Philippines. Research targeting MSM, PWID, and transgender populations is needed to understand the transmission risk factors and specific structural, social, behavioral, and epidemiological factors impacting these groups. While there is a considerable body of HIV prevention intervention research focusing on MSM and PWIDs in other parts of the world [ 63 , 64 ], none have been specific to the Philippines. It remains unclear whether existing prevention interventions are adaptable or require distinct design for this national context. Additionally, despite an estimated global HIV prevalence of 19% [ 65 ], and anecdotal reports that suggests a growing burden of HIV among transgender women in the Philippines [ 66 ], none of the included studies have focused on or included this key population. It is possible that researchers in the Philippines have aggregated transgender populations within the MSM rubric [ 67 ]. Given HIV epidemiological trends within the Philippines and evidence from other settings about the disproportionate prevalence of HIV among transgender people, future research must disaggregate transgender and MSM populations and resist the conflation of gender and sexual identities [ 68 ]. Additionally, given that UNAIDS surveillance data points to youth and young adults being affected [ 2 ], more biological and behavioral research data and interventions are necessary to understand the epidemic among youth and young adults in the Philippines, especially those who are also members of MSM, PWID, or transgender populations.

Most of the studies identified in this review used cross-sectional surveys with convenience samples, involving mostly descriptive measures, which limit the generalizability of the research. While these study designs are useful in exploratory investigations, it is imperative for researchers to increase the rigor of investigations by using longitudinal and experimental studies in order to examine more complex research hypotheses (e.g., testing hypotheses about social-behavioral determinants of HIV infection) and to test interventions [ 68 ].

Moreover, as the majority of includes studies were conducted prior 2008, researchers must also examine biomedical factors that might determine or mitigate the growth of HIV in the Philippines–e.g., factors associated with medication adherence and viral load suppression among PLHIV (i.e., treatment-as-prevention), access to and use of biomedical prevention such as post-exposure prophylaxis and pre-exposure prophylaxis, home-based testing, and male-circumcision. Given the political climate regarding drug use in the Philippines, the viability of harm reduction and needle exchange programs for HIV prevention must be carefully considered [ 69 , 70 ].

The literature identified in this review was also noteworthy with regard to the scarcity of investigation into psychosocial and ecological factors that contribute to HIV risk, mental health, personal and community empowerment, stigma, and substance use. While it is important to continue assessing condom use-related measures in key populations, it is imperative that researchers examine contextual conditions and co-morbid health factors associated with low condom use as well as the broader social-structural drivers of HIV risk and infection, in order to understand factors affecting the acceptability and feasibility of bio-behavioral preventative strategies.

Taken together, these findings provide initial insight into the increasing and shifting HIV epidemic in the Philippines, from an initial concentration among FSWs to including populations such as MSM and PWIDs. These findings also suggest the need to develop social-contextual frameworks to prioritize HIV prevention strategies and contextualize HIV risk/prevention according to the lived experiences of key populations. Assessment of clinical and service provider capacities in responding to HIV risk and infections is also important to guide research and build a stronger public health infrastructure.

Limitations of this review must be considered. First, although this review followed a systematic search protocol and a priori inclusion criteria, it is possible that not all relevant articles were identified. Second, meta-analysis was not deemed appropriate due to heterogeneity in samples, methods, measures, and time of data collection. Third, the review included only English-language publications. Fourth, the generalizability of the review might be limited given the specificity of the context for this review and the ongoing evolution of the Philippines’ national epidemic.

This is the first known systematic review to provide evidence about and identify gaps in published research about risk groups, risk factors, and intervention approaches addressing the Philippine’s HIV epidemic. Studies revealed a nascent body of literature, especially with regard to intervention research, biomedical prevention, and key populations currently impacted by the HIV epidemic such as PWIDs, MSM, and transgender populations. Future HIV research studies in the Philippines must use rigorous research methodologies including purposeful sampling strategies and validated measures (including biological assessments for HIV and STIs, and established measures for substance use, condom use, and mental health). Furthermore, given the evolving epidemic in the Philippines, researchers should capitalize on opportunities to implement and evaluate bio-behavioral intervention strategies including pre-exposure prophylaxis, treatment-as-prevention, and regular HIV testing with key populations. Use of online data recruitment and data collection approaches can improve access to hard-to-reach or remote populations; online research might be especially useful for reaching members of historically stigmatized groups. A multi-disciplinary research agenda for understanding and addressing HIV transmission in the Philippines must span across various domains of research including prevention, epidemiology, treatment, and behavioral and social science.

Supporting information

S1 fig. prisma checklist (2009)..

https://doi.org/10.1371/journal.pone.0207663.s001

Acknowledgments

Study was supported by National Institute of Health (NIH)-Fogarty D43TW010565, NIH-NIAID P30AI042853, Brown University Global Health Scholars program, and the Robert Wood Johnson Foundation Health Policy Research Scholars program (awarded to Arjee Restar). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, Brown University, nor RWJF.

• View Article
• Google Scholar
• 2. Joint United Nations Programme on HIV/AIDS (UNAIDS). (2017). UNAIDS Data 2017. Available at: http://www.unaids.org/sites/default/files/media_asset/20170720_Data_book_2017_en.pdf
• 3. Philippines Department of Health. HIV/AIDS and ART Registry of the Philippines: Newly Diagnosed HIV cases in the Philippines. Philippines Department of Health Bureau of Epidemiology; 2017.
• 4. Joint United Nations Programme on HIV/AIDS [UNAIDS]. Global AIDS Response Progress Reporting: Country Progress Report Philippines. UNAIDS; 2014.
• PubMed/NCBI
• 7. World Health Organization. External review of the national health sector response to HIV and sexually transmitted infections 2013: Republic of the Philippines. Manila: WHO Regional Office for the Western Pacific; 2015.
• 8. Pew Research Center. Pew-Templeton Global Religious Futures Project: Philippines Religious Affliation. Pew Research Center; 2016.
• 9. Santons A. The city at the heart of the Philippines’ HIV epidemic: The Atlantic; 2016 [Available from: https://www.theatlantic.com/health/archive/2016/01/cebu-city-philippines-hiv-drugs/422700/ .
• 19. Balk D. Are young people in the Philippines taking chances with HIV/AIDS? 1997.
• 66. World Health Organization. Transgender Health and HIV in the Philippines. WHO Representative Office: Philippines; 2016.

• 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

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.

• Open access
• Published: 20 October 2006

A reflection on HIV/AIDS research after 25 years

• Robert C Gallo 1  

Retrovirology volume  3 , Article number:  72 ( 2006 ) Cite this article

57k Accesses

63 Citations

32 Altmetric

Metrics details

Dr. Robert C. Gallo provides a personal reflection on the 25 year history of AIDS.

A reflection on the 25 year history of AIDS can begin with no better outline than that provided by the late Jonathan Mann of WHO. A slide he gave to me in the late 1980's divides the history of AIDS into four periods: (see fig. 1 ). Jonathan could not know that the period of silent spread (part 1 of this saga) of HIV actually began years earlier. We now know that, by 1971, the virus had moved to several different regions of the world, but exactly when it came out of Africa is conjectural.

A summary of the five periods of AIDS history as modified after Jonathan Mann.

There has been considerable attention (no less than three papers in Science and Nature over the past few years from B. Hahn and her colleagues) that the natural reservoir for HIV-1 is a particular subspecies of chimp [ 1 – 3 ]. The primate-to-man origin of HIV was suspected almost from the beginning, albeit without knowing which primate. The reasons were three fold: 1) the early evidence that HIV was widespread in central Africa; 2) the evidence that HIV was more variable in Africa (hence longer presence); and 3) prior experience with HTLV-1 and HTLV-2 and their related retroviruses in African and Asian primates (STLV strains), especially the evidence suggesting a chimp origin of HTLV-1, coupled with the discovery of SIV by scientists in Boston, and later of many other strains identified in various African but not Asian monkeys. Human sera reacted better with some of these SIV strains from West Africa than they did with HIV-1, giving impetus to the work that led to the finding of HIV-2, and the obvious conclusion that HIV-2 came into man from these monkeys (sooty mangabey) [ 4 ].

But, how did the original infection of people in rainforests become an epidemic? Here we must rely on history. I presume people in rainforests (especially hunters) were occasionally infected for a long time, but died with their disease. Migration to cities may have been associated with increased prostitution. The movement of the rainforests to the world can be seen as the consequence of post World War II societal changes: increased travel with increased promiscuity, advancing intravenous drug addiction, and blood and blood products moving from one nation to another for medical purposes.

Part 2 (Fig. 1 ) is the identification of the disease by U.S. clinicians (1981) [ 5 – 7 ], and defining it as an immune disorder characterized by a decline of immune function and of T cells, and notably CD4 T cells, and by 1982 the identification of risk groups then called the "4 H's" (hemophiliacs, heroin addicts, homosexuals and Haitians). It is in the period (1982) when my colleagues and I began to think about this problem, and we initiated our first experiments in May 1982.

Along with Max Essex in Boston, I speculated in early 1982 that AIDS would be caused by a retrovirus. This was based on information that some retroviruses, like feline leukemia virus (FeLV), caused not only leukemia, but blood cell deficiencies including those of T cells [ 8 ]. This was apparently associated with genetic changes in the FeLV envelope. More importantly, I was influenced by our experiences with human retroviruses (HTLV-1 and HTLV-2), which we had only recently discovered [ 9 – 11 ]. The reasons were six fold: 1) HTLV-1 and HTLV-2 mainly targeted CD4 T cells; 2) we knew they were transmitted by blood, sex, and mother to infant especially by breast feeding. These were precisely the suggested modes of transmission of the putative microbial cause of AIDS suggested by James Curran of the U.S. Centers for Disease Control (CDC); 3) HTLV's were endemic in parts of Africa and in Haiti, and CDC had announced these were hot-beds for AIDS; 4) we knew that, even in the absence of leukemia, HTLV-1 could cause minor immune impairment; 5) we had just discovered HTLV-1 and HTLV-2, so why not a 3 rd human retrovirus, and one with the capacity to cause a profound immune disorder? 6) finally, as we began this work somewhat tentatively, I was encouraged by David Baltimore, who independently wondered aloud to me that a retrovirus was probably the origin of AIDS.

The idea, however, has sometimes been misunderstood and misrepresented as our hypothesizing that HTLV-1 itself was the cause of AIDS. That is clearly not the case. Our idea was that AIDS would be caused by a new retrovirus , but one in the HTLV family. At the time, there were at least a dozen theories as to the cause of AIDS, including non-infectious causes. Our hypothesis was the one that bore fruit. As we soon learned to our astonishment, HIV would be in a separate family of retroviruses.

J. Mann's Part 3 of AIDS history are the years 1983–85. He called this the period of intense discovery. It begins with the isolation of HIV. Our approach to find the virus of AIDS was to follow our successful pattern with the HTLV's, namely, the culture of blood cells from patients, activation of the T cells in these samples, growth of the T cells with IL-2, and search for reverse transcriptase actively in the supernatant. If positive, we would look for some cross reactivity with HTLV-1 or HTLV-2 with antibodies to proteins of these viruses. Concomitantly, we probed DNA and RNA of some primary tissues of AIDS patients using cDNA from HTLV-1 under rather relaxed conditions in order to detect sequences that might be related to HTLV-1 and 2. In 1982 and in early 1983, these experiments gave variable results that were sometimes highly positive, other times borderline or even negative. In retrospect, the highly positive samples (with sequences related to HTLV) were due to patients being doubly infected with HTLV-1 or HTLV-2 plus HIV, which occurred in close to 10% of our samples. Negative or borderline RT positive samples were due to our performing the RT assays later than the optimal peak of virus production, which occurs days earlier with HIV than with HTLV. Luc Montagnier was stimulated in part by our ideas brought to France by the French clinician Jacques Leibowitch and, in early 1983, I sent Montagnier IL-2 and antibodies against the HTLV's. He and his co-workers had found evidence of a retrovirus in a patient with lymphadenopathy, and they could distinguish it from the HTLV-1 and with those antibodies [ 12 ]. This was the first "clean" finding of HIV. Our samples at that time always had HTLV-1 as the dominant virus. However, by mid 1983, we were able to obtain many isolates of HIV, and by the time we published our papers (May 4, 1984) we described isolates from 48 patients [ 13 ]. Importantly, we were able to put six of these isolates into continuously growing T cell lines [ 14 ].

This was the necessary breakthrough, because for the first time there would be sufficient virus for detailed characterization and the development of a workable HIV blood test. The blood test (for serum antibodies to HIV), along with the large number of isolates from AIDS patients, were the major convincing results that HIV (which at the time we called HTLV-III and the French group called LAV) was the causative agent of AIDS [ 15 ].

Demonstrating that HIV was the cause of AIDS provided some special challenges – unlike most viral infections. The first was the long period between infection and the signs of AIDS (5 to 15 years). Physicians and public health officials do not ask a patient what they did a decade earlier, but rather think in terms of days or weeks. The second was the numerous infections a patient develops as they present with AIDS. Which one, if any, was the cause? The third was our concerns about verification. For rapid progress, it was essential to have rapid verification, and there were at least two factors that could greatly prolong achieving this goal. (1) Samples from AIDS patients were not only limited, but some institutions had forbade even their entry due to fears of infection. (2) T-cell culture technology, though available in immunology laboratories, was not widely available in virology laboratories. Both of these restrictions made it unlikely that there would be sufficiently rapid and conclusive confirmation by HIV isolation. Consequently, the blood test seemed to us to be particularly urgent for three reasons: 1) it allowed prevention of HIV transmission from contaminated blood; 2) it opened the door to our ability to follow the epidemic from the early period of infection, and 3) it provided for verification of HIV's causative role in AIDS. The test for serum antibodies was simple, inexpensive, safe, rapid, sensitive and accurate. Consequently, verification came rapidly and globally.

A problem then occurred that enormously hindered our work over the coming years. One of our culture samples became contaminated with virus sent to us by Luc Montagnier. At first we stubbornly refused to believe that this was possible, because the strain of HIV from Paris had different characteristics in cell culture. However, this has now been clarified [ 16 , 17 ]. Montagnier had unknowingly sent us a very different strain of HIV that grows well in cell lines. This strain contaminated his culture of LAV before it contaminated one of ours.

Then, from all sides and in big doses, came patent suits over royalties to the blood test, lawyers, media, politics and just plain pressure. Meanwhile, there were other odd problems such as people who denied the existence of AIDS, others who believed HIV did not exist, groups who believed HIV existed, but didn't cause AIDS, and those who believed HIV existed, caused AIDS, and was developed in a U.S. laboratory to kill African Americans and gay men. Suffice it to say, no scientist is prepared for things like this. Despite these distractions, science progressed with great speed. Mann called it the fastest pace of discovery in medical history from the time of inception of a new disease.

To briefly revisit that period, some of the noteworthy advances are listed here. They include discovery of HIV (1983–84) [ 12 – 14 ]; convincing evidence that it was the cause of AIDS ('84) [ 15 , 18 , 19 ]; modes of transmission understood ('84–'85); genome sequenced ('85) [ 20 – 22 ]; most genes and proteins defined ('84–'85) though not all their functions[ 23 – 25 ]; main target cells CD4 T cells, macrophages, and brain microglial cells – elucidated [ 26 , 27 ]; key reagents produced and made available for involved scientists all over the world ('84–'85); genomic heterogeneity of HIV ('84) – including the innumerable microvariants within a single patient ('86–'88) [ 28 , 29 ], first practical life saving advance ('85); the blood test ('84)[ 30 ]; close monitoring of the epidemic for the first time, because of the wide availability of the blood test ('85); the SIV-monkey model ('85) [ 31 , 32 ]; the beginning of therapy – AZT ('85)[ 33 ]; and the beginning understanding of pathogenesis ('85)[ 34 ].

These rapid advances led to expectations that AIDS might be quickly solved. However, those scientists with experience in retrovirology knew differently: Unless a successful vaccine was soon available, this would be a long road – an infection that might be permanent in the population as retroviruses are in many species. Furthermore, we knew by mid-1984 that the infection was becoming global. We had tested sera from many countries, and we could follow the evidence for HIV coming into a region (a positive HIV blood test) with subsequent AIDS. However, we could never anticipate the HIV African tragedy.

Despite the rapid advances in those years, I think it is still appropriate to ask whether we could have done better. For example, were we as medical scientists, health officials, doctors or simply as members of society prepared? The answer is an interesting mix of opposites! On the one hand, if AIDS had to come, we were lucky that (scientifically speaking) it came at a very good time. The 1970's saw the revelation of the replication cycle of animal retroviruses (so we had a framework to work by once HIV was established as the cause). We had most modern tools of molecular biology (mainly developed in the 1970's). We had monoclonal antibodies also developed in the 1970's. We had access to technology to grow human T-cells with IL-2 which my colleagues and I developed in the mid-1970's, and we had found other human retroviruses in the 1980's-82 giving the first credence to their presence in humans. However, if AIDS had to come, we could also say it came at the worst of times. It seems that people have a memory span not longer than 25–30 years. Here are three examples of what I mean: First, was the surprise and lack of preparation in 1918–1919 for the great influenza epidemic – forgetting lessons of the late 19 th century [ 35 ]. Secondly, there was surprise and lack of preparation at the onset of the polio epidemic in the late 1940's and early 1950's [ 36 ]. It is eerie to read accounts of that period showing that medical science in particular and society as a whole, were focused on chronic degenerative diseases, believing serious infectious diseases to be "conquered". Eerie also because, thirdly that was precisely the attitude once again by the late 1970's evidenced by the closure of some microbiology departments, and threats of increasing reductions to CDC. The microbe would be simply the playground of the molecular biologist. Some even felt humans could not be infected by retroviruses.

No group was really responsible for unraveling the cause of the new epidemic, except the CDC, but in my view the CDC cannot and does not have expertise in every class of microbes, let alone for all types of viruses, and indeed they had no expertise in animal or human retroviruses. Our group became involved only after I listened to a lecture by the CDC's James Curran, who called for help from virologists. I have suggested that the government provide base support for 10 or more virus centers, covering all types of viruses among the centers. These centers would be responsible for providing needed expertise to the CDC for the etiological agent, diagnostics and possibly therapy and prevention. In accordance with the kind of virus suspected, the center(s) would be activated. Each center might also be required to have close collaborations with at least two groups from developing nations.

Though the HIV blood test was brought forward rapidly (early 1985) to large companies that could make the test available on an industrialized scale, I believe we could have still done better. For instance, we could have tested the pooled plasma used for hemophiliacs in 1984 without a large industrial scale production of the test. I don't think anyone was thinking of this. We were advised to return to basic laboratory research and assumed someone would be doing these tests. The lesson here for me is to take more control of things that come from your own work.

Where did things go since this early period of 1982–85? Jonathan Mann describes Part 4 ('86) as the time of global mobilization. This means education leading to prevention of infection, and no doubt this was the second major practical advance and it continues today with results that vary in place and even in time. There is proven success in some places, but not all, and sometimes there is only temporary success. It is noteworthy that appropriate education also depends upon the blood test, hence on basic science.

There were many other major advances over these next 20 years ('86-06), but none were more important than therapy. This is listed as Part 5 of Mann's summary, but it was added by me as the "period" era of practical advances, but the time lines for these advances are actually from 1984–1995. AZT showed for the first time that a viral disease could be objectively treated (decline in virus levels and lessened signs of AIDS), and there is no need to embellish here on the great advances made with the triple drug therapy in the mid 1990's. This was from contributions of a great number of scientists: those who contributed to our basic understanding of HIV replication, and as a result to targets for therapy, and those who developed the culture systems to grow HIV that could also be used in drug testing, and of course to the pharmaceutical industry, especially those like E. Emini who helped design and develop the protease inhibitors.

The other major practical advances in the last two decades have mainly been an extension of the earlier ones: more widespread use of the blood test as well as educational programs; refining therapies; learning about HIV drug resistance and how best to avoid it; better care of patients; and learning about serious co-infections especially of tuberculosis and HCV. A selection of the most important basic science advances will be debatable. In my view, the most important include the following: clarification of the two HIV strain functional extremes – the pure CCR5 tropic viruses and the CXCR4 tropic viruses [ 37 – 42 ], for review, see [ 43 , 44 ]; the discovery of the first endogenous inhibitors of HIV (β-chemokines) [ 44 ]; elucidation of the mechanisms involved in the action of some the HIV non-structural proteins [ 45 , 46 ]; an appreciation of the role of abnormal immune activation in pathogenesis, which impacts not only HIV infected cells, but is also detrimental to uninfected immune cells for review, see [ 44 , 47 ]; major advances in our understanding of the various types of HIV in different regions of the world and new recombinant forms; evolving knowledge of the envelope structure [ 48 , 49 ]; the details of HIV entry into cells [ 50 ]; and various genetic and some environmental mechanisms for resisting infection and slowing progression to AIDS in infected persons, as well others fostering infection and progression [ 51 , 52 ]. These latter basic advances have already had their practical impact, including for example several new approaches for drugs that target HIV entry.

We have reached the end of the first 25 years of AIDS, and we can safely say that we know as much about HIV as we do of any pathogen and about AIDS as we do any human disease. The remaining problems and needs are evident: bringing therapy and better health infrastructure to poor nations; continuing to develop new treatments because of the need for life-long therapy and the associated drug side effects and HIV resistance; continuing and advancing education; global monitoring of the different strains of HIV for changes in their virulence, transmissibility and drug resistance; and development of a preventive vaccine which provides sterilizing immunity (or close to it) [ 53 ]. For a successful vaccine, I believe we need neutralizing antibodies that are sustained (do not need rapid recall), and I think this is a reachable objective. Parenthetically, it has often been erroneously said (most recently in the New York Times reporting of the Toronto International AIDS Conference) that, at the April 1984 press conference, Secretary of Health, Margaret Heckler stated that a successful vaccine would be available within two years. Transcripts of comments are still available and show that no such claim was made. Rather, it was said that the virus could be continuously produced in large amounts, thereby making trials possible within two years. Indeed, this proved true, because in 1986, Daniel Zagury carried out some phase 1 trials in Africa and in Paris.

Several encouraging developments provide some optimism for the future, such as the ability of some nations to diminish rates of infection by education, and major new funding sources aimed at practical achievements. One laudable example is President Bush's Emergency Plan for AIDS Relief, which is providing $15 billion for therapy for HIV positive patients in needy nations. We have been impressed that this effort carries out its mission with leadership by university clinical scientists who work with groups with long experience in the specific country. In contrast to alternative plans that simply and rapidly provide funds for the drugs, these programs add to local infrastructure and training, thereby reducing the prospects for creating more multi-drug resistant HIV mutants. Private foundations have also been a new forceful addition; International AIDS Vaccine Initiative (IAVI) for developing vaccine candidates and the Bill and Melinda Gates Foundation for fulfilling many needs.

There are also major concerns for the future. We know science is essential for solving the HIV problem and, as noted before, science has been responsible for all the major practical advances in fighting this disease. However, there is a growing distance between scientists and the larger public. John Moore of Cornell Weill Medical School reminded me that C.P. Snow wrote about this in the 1950's, but I think the gap has continued to widen as technology becomes more and more specialized. Sometimes, it leads to tension and even hostility by the larger public toward scientists. This is sometimes evident in AIDS, seemingly so in recent years. Consider a recent CNN program that was a positive educational force, but advertised as one composed of AIDS experts. However, not one scientist was among the experts, and the program ended with a movie actor stating that to solve the problem, we all "had to be together." It was togetherness rather than science that he informed us would solve AIDS.

To return to and end on a positive note: it is interesting and useful to remember that there has been some silver lining on the dark AIDS clouds. Consider the many positive spin-offs to science in immunology, cancer biology, basic virology, and even molecular biology along with the leadership and focus AIDS research has provided to therapy of viral infections and to vaccine development. Positive spin-offs have not been limited to science. Consider how AIDS has inspired far greater tolerance (at least in the West) of differences in sexuality and much greater scientific and humanitarian collaborations between developed and less developed nations. Certainly, this is the case for relations between the U.S. and Africa. Let us hope these advances in understanding and in conscience will continue to evolve and grow so that there will be no need for anyone to reflect on AIDS in its 50 th birthday year.

Gao F, Bailes E, Robertson DL, Chen Y, Rodenburg CM, Michael SF, Cummins LB, Arthur LO, Peeters M, Shaw GM, Sharp PM, Hahn BH: Origin of HIV-1 in the chimpanzee Pan troglodytes troglodytes. Nature. 1999, 397: 436-441. 10.1038/17130.

Article   CAS   PubMed   Google Scholar  

Keele BF, Van HF, Li Y, Bailes E, Takehisa J, Santiago ML, Bibollet-Ruche F, Chen Y, Wain LV, Liegeois F, Loul S, Ngole EM, Bienvenue Y, Delaporte E, Brookfield JF, Sharp PM, Shaw GM, Peeters M, Hahn BH: Chimpanzee reservoirs of pandemic and nonpandemic HIV-1. Science. 2006, 313: 523-526. 10.1126/science.1126531.

Article   PubMed Central   CAS   PubMed   Google Scholar  

Santiago ML, Rodenburg CM, Kamenya S, Bibollet-Ruche F, Gao F, Bailes E, Meleth S, Soong SJ, Kilby JM, Moldoveanu Z, Fahey B, Muller MN, Ayouba A, Nerrienet E, McClure HM, Heeney JL, Pusey AE, Collins DA, Boesch C, Wrangham RW, Goodall J, Sharp PM, Shaw GM, Hahn BH: SIVcpz in wild chimpanzees. Science. 2002, 295: 465-10.1126/science.295.5554.465.

Sharp PM, Bailes E, Chaudhuri RR, Rodenburg CM, Santiago MO, Hahn BH: The origins of acquired immune deficiency syndrome viruses: where and when?. Philos Trans R Soc Lond B Biol Sci. 2001, 356: 867-876. 10.1098/rstb.2001.0863.

Siegal FP, Lopez C, Hammer GS, Brown AE, Kornfeld SJ, Gold J, Hassett J, Hirschman SZ, Cunningham-Rundles C, Adelsberg BR: Severe acquired immunodeficiency in male homosexuals, manifested by chronic perianal ulcerative herpes simplex lesions. N Engl J Med. 1981, 305: 1439-1444.

Gottlieb MS, Schroff R, Schanker HM, Weisman JD, Fan PT, Wolf RA, Saxon A: Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiency. N Engl J Med. 1981, 305: 1425-1431.

Friedman-Kien AE: Disseminated Kaposi's sarcoma syndrome in young homosexual men. J Am Acad Dermatol. 1981, 5: 468-471.

Wernicke D, Trainin Z, Ungar-Waron H, Essex M: Humoral immune response of asymptomatic cats naturally infected with feline leukemia virus. J Virol. 1986, 60: 669-673.

PubMed Central   CAS   PubMed   Google Scholar  

Kalyanaraman VS, Sarngadharan MG, Robert-Guroff M, Miyoshi I, Golde D, Gallo RC: A new subtype of human T-cell leukemia virus (HTLV-II) associated with a T-cell variant of hairy cell leukemia. Science. 1982, 218: 571-573. 10.1126/science.6981847.

Poiesz BJ, Ruscetti FW, Gazdar AF, Bunn PA, Minna JD, Gallo RC: Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci U S A. 1980, 77: 7415-7419. 10.1073/pnas.77.12.7415.

Poiesz BJ, Ruscetti FW, Reitz MS, Kalyanaraman VS, Gallo RC: Isolation of a new type C retrovirus (HTLV) in primary uncultured cells of a patient with Sezary T-cell leukaemia. Nature. 1981, 294: 268-271. 10.1038/294268a0.

Barre-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, Dauguet C, Axler-Blin C, Vezinet-Brun F, Rouzioux C, Rozenbaum W, Montagnier L: Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science. 1983, 220: 868-871. 10.1126/science.6189183.

Gallo RC, Salahuddin SZ, Popovic M, Shearer GM, Kaplan M, Haynes BF, Palker TJ, Redfield R, Oleske J, Safai B: Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS. Science. 1984, 224: 500-503. 10.1126/science.6200936.

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. 10.1126/science.6200935.

Sarngadharan MG, Popovic M, Bruch L, Schupbach J, Gallo RC: Antibodies reactive with human T-lymphotropic retroviruses (HTLV-III) in the serum of patients with AIDS. Science. 1984, 224: 506-508. 10.1126/science.6324345.

Wain-Hobson S, Vartanian JP, Henry M, Chenciner N, Cheynier R, Delassus S, Martins LP, Sala M, Nugeyre MT, Guetard D: LAV revisited: origins of the early HIV-1 isolates from Institut Pasteur. Science. 1991, 252: 961-965. 10.1126/science.2035026.

Guo HG, Chermann JC, Waters D, Hall L, Louie A, Gallo RC, Streicher H, Reitz MS, Popovic M, Blattner W: Sequence analysis of original HIV-1. Nature. 1991, 349: 745-746. 10.1038/349745a0.

Schupbach J, Popovic M, Gilden RV, Gonda MA, Sarngadharan MG, Gallo RC: Serological analysis of a subgroup of human T-lymphotropic retroviruses (HTLV-III) associated with AIDS. Science. 1984, 224: 503-505. 10.1126/science.6200937.

Safai B, Sarngadharan MG, Groopman JE, Arnett K, Popovic M, Sliski A, Schupbach J, Gallo RC: Seroepidemiological studies of human T-lymphotropic retrovirus type III in acquired immunodeficiency syndrome. Lancet. 1984, 1: 1438-1440. 10.1016/S0140-6736(84)91933-0.

Sanchez-Pescador R, Power MD, Barr PJ, Steimer KS, Stempien MM, Brown-Shimer SL, Gee WW, Renard A, Randolph A, Levy JA: Nucleotide sequence and expression of an AIDS-associated retrovirus (ARV-2). Science. 1985, 227: 484-492. 10.1126/science.2578227.

Ratner L, Haseltine W, Patarca R, Livak KJ, Starcich B, Josephs SF, Doran ER, Rafalski JA, Whitehorn EA, Baumeister K: Complete nucleotide sequence of the AIDS virus, HTLV-III. Nature. 1985, 313: 277-284. 10.1038/313277a0.

Wain-Hobson S, Sonigo P, Danos O, Cole S, Alizon M: Nucleotide sequence of the AIDS virus, LAV. Cell. 1985, 40: 9-17. 10.1016/0092-8674(85)90303-4.

Arya SK, Gallo RC, Hahn BH, Shaw GM, Popovic M, Salahuddin SZ, Wong-Staal F: Homology of genome of AIDS-associated virus with genomes of human T-cell leukemia viruses. Science. 1984, 225: 927-930. 10.1126/science.6089333.

Muesing MA, Smith DH, Cabradilla CD, Benton CV, Lasky LA, Capon DJ: Nucleic acid structure and expression of the human AIDS/lymphadenopathy retrovirus. Nature. 1985, 313: 450-458. 10.1038/313450a0.

Robey WG, Safai B, Oroszlan S, Arthur LO, Gonda MA, Gallo RC, Fischinger PJ: Characterization of envelope and core structural gene products of HTLV-III with sera from AIDS patients. Science. 1985, 228: 593-595. 10.1126/science.2984774.

Harper ME, Marselle LM, Gallo RC, Wong-Staal F: Detection of lymphocytes expressing human T-lymphotropic virus type III in lymph nodes and peripheral blood from infected individuals by in situ hybridization. Proc Natl Acad Sci U S A. 1986, 83: 772-776. 10.1073/pnas.83.3.772.

Shaw GM, Hahn BH, Arya SK, Groopman JE, Gallo RC, Wong-Staal F: Molecular characterization of human T-cell leukemia (lymphotropic) virus type III in the acquired immune deficiency syndrome. Science. 1984, 226: 1165-1171. 10.1126/science.6095449.

Saag MS, Hahn BH, Gibbons J, Li Y, Parks ES, Parks WP, Shaw GM: Extensive variation of human immunodeficiency virus type-1 in vivo. Nature. 1988, 334: 440-444. 10.1038/334440a0.

Hahn BH, Shaw GM, Taylor ME, Redfield RR, Markham PD, Salahuddin SZ, Wong-Staal F, Gallo RC, Parks ES, Parks WP: Genetic variation in HTLV-III/LAV over time in patients with AIDS or at risk for AIDS. Science. 1986, 232: 1548-1553. 10.1126/science.3012778.

Joyce C, Anderson I: US licenses blood test for AIDS. New Sci. 1985, 105: 3-4.

PubMed   Google Scholar  

Chakrabarti L, Guyader M, Alizon M, Daniel MD, Desrosiers RC, Tiollais P, Sonigo P: Sequence of simian immunodeficiency virus from macaque and its relationship to other human and simian retroviruses. Nature. 1987, 328: 543-547. 10.1038/328543a0.

Chalifoux LV, Ringler DJ, King NW, Sehgal PK, Desrosiers RC, Daniel MD, Letvin NL: Lymphadenopathy in macaques experimentally infected with the simian immunodeficiency virus (SIV). Am J Pathol. 1987, 128: 104-110.

Mitsuya H, Weinhold KJ, Furman PA, St Clair MH, Lehrman SN, Gallo RC, Bolognesi D, Barry DW, Broder S: 3'-Azido-3'-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro. Proc Natl Acad Sci U S A. 1985, 82: 7096-7100. 10.1073/pnas.82.20.7096.

Lane HC, Fauci AS: Immunologic abnormalities in the acquired immunodeficiency syndrome. Annu Rev Immunol. 1985, 3: 477-500. 10.1146/annurev.iy.03.040185.002401.

Barry JM: The Great Influenza: The Epic Story of the Deadliest Plague in History. 2004, New York, NY, Viking

Google Scholar  

Oshinsky DM: Polio: An American Story. 2005, New York, NY, Oxford University Press

Dragic T, Litwin V, Allaway GP, Martin SR, Huang Y, Nagashima KA, Cayanan C, Maddon PJ, Koup RA, Moore JP, Paxton WA: HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature. 1996, 381: 667-673. 10.1038/381667a0.

Doranz BJ, Rucker J, Yi Y, Smyth RJ, Samson M, Peiper SC, Parmentier M, Collman RG, Doms RW: A dual-tropic primary HIV-1 isolate that uses fusin and the beta- chemokine receptors CKR-5, CKR-3, and CKR-2b as fusion cofactors. Cell. 1996, 85: 1149-1158. 10.1016/S0092-8674(00)81314-8.

Deng H, Liu R, Ellmeier W, Choe S, Unutmaz D, Burkhart M, Di Marzio P, Marmon S, Sutton RE, Hill CM, Davis CB, Peiper SC, Schall TJ, Littman DR, Landau NR: Identification of a major co-receptor for primary isolates of HIV-1. Nature. 1996, 381: 661-666. 10.1038/381661a0.

Choe H, Farzan M, Sun Y, Sullivan N, Rollins B, Ponath PD, Wu L, Mackay CR, LaRosa G, Newman W, Gerard N, Gerard C, Sodroski J: The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. Cell. 1996, 85: 1135-1148. 10.1016/S0092-8674(00)81313-6.

Alkhatib G, Combadiere C, Broder CC, Feng Y, Kennedy PE, Murphy PM, Berger EA: CC CKR5: a RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for macrophage-tropic HIV-1. Science. 1996, 272: 1955-1958.

Feng Y, Broder CC, Kennedy PE, Berger EA: HIV-1 entry cofactor: functional cDNA cloning of a seven- transmembrane, G protein-coupled receptor. Science. 1996, 272: 872-877.

Lusso P: HIV and the chemokine system: 10 years later. EMBO J. 2006, 25: 447-456. 10.1038/sj.emboj.7600947.

Cocchi F, DeVico AL, Garzino-Demo A, Arya SK, Gallo RC, Lusso P: Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells. Science. 1995, 270: 1811-1815.

Feinberg MB, Jarrett RF, Aldovini A, Gallo RC, Wong-Staal F: HTLV-III expression and production involve complex regulation at the levels of splicing and translation of viral RNA. Cell. 1986, 46: 807-817. 10.1016/0092-8674(86)90062-0.

Sodroski J, Rosen C, Wong-Staal F, Salahuddin SZ, Popovic M, Arya S, Gallo RC, Haseltine WA: Trans-acting transcriptional regulation of human T-cell leukemia virus type III long terminal repeat. Science. 1985, 227: 171-173. 10.1126/science.2981427.

Ascher MS, Sheppard HW: AIDS as immune system activation: a model for pathogenesis. Clin Exp Immunol. 1988, 73: 165-167.

Chan DC, Fass D, Berger JM, Kim PS: Core structure of gp41 from the HIV envelope glycoprotein. Cell. 1997, 89: 263-273. 10.1016/S0092-8674(00)80205-6.

Kwong PD, Wyatt R, Robinson J, Sweet RW, Sodroski J, Hendrickson WA: Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature. 1998, 393: 648-659. 10.1038/31405.

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: 763-767. 10.1038/312763a0.

Dean M, Jacobson LP, McFarlane G, Margolick JB, Jenkins FJ, Howard OM, Dong HF, Goedert JJ, Buchbinder S, Gomperts E, Vlahov D, Oppenheim JJ, O'Brien SJ, Carrington M: Reduced risk of AIDS lymphoma in individuals heterozygous for the CCR5- delta32 mutation. Cancer Res. 1999, 59: 3561-3564.

CAS   PubMed   Google Scholar  

Martin MP, Dean M, Smith MW, Winkler C, Gerrard B, Michael NL, Lee B, Doms RW, Margolick J, Buchbinder S, Goedert JJ, O'Brien TR, Hilgartner MW, Vlahov D, O'Brien SJ, Carrington M: Genetic acceleration of AIDS progression by a promoter variant of CCR5. Science. 1998, 282: 1907-1911. 10.1126/science.282.5395.1907.

Gallo RC: The end or the beginning of the drive to an HIV-preventive vaccine: a view from over 20 years. Lancet. 2005, 366: 1894-1898. 10.1016/S0140-6736(05)67395-3.

Article   PubMed   Google Scholar  

Download references

Acknowledgements

I am deeply grateful to my long time colleague, Dr. Marvin Reitz, for his reading of this manuscript and help with references. I thank Ms. Risa Davis for her editorial assistance.

Author information

Authors and affiliations.

Institute of Human Virology, University of Maryland Biotechnology Institute and Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, 21201, USA

Robert C Gallo

You can also search for this author in PubMed   Google Scholar

Corresponding author

Correspondence to Robert C Gallo .

Authors’ original submitted files for images

Below are the links to the authors’ original submitted files for images.

Authors’ original file for figure 1

Rights and permissions.

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and permissions

About this article

Cite this article.

Gallo, R.C. A reflection on HIV/AIDS research after 25 years. Retrovirology 3 , 72 (2006). https://doi.org/10.1186/1742-4690-3-72

Download citation

Received : 04 October 2006

Accepted : 20 October 2006

Published : 20 October 2006

DOI : https://doi.org/10.1186/1742-4690-3-72

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

• Melinda Gate Foundation
• Triple Drug Therapy
• Feline Leukemia Virus
• Large Industrial Scale Production
• Successful Vaccine

View archived comments (1)

Retrovirology

ISSN: 1742-4690

• Submission enquiries: [email protected]

• 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

10k 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.

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.

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.).

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: [email protected]
• General enquiries: [email protected]

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.

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.

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

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.

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.

Custom Essay, Term Paper & Research paper writing services

• testimonials

Toll Free: +1 (888) 354-4744

Email: [email protected]

Writing custom essays & research papers since 2008

How to write a hiv research paper.

Writing an HIV research paper requires extensive research and understanding of the available data. HIV/AIDS is among the most challenging diseases that humankind has ever faced. When pursuing medical studies, a student will most likely be asked to write a research paper about aids. That’s because educators want learners to understand different aspects of this disease and some of the ways to resolve them.

Researching and writing about HIV/AIDS is not easy. A learner has to search books, journals, and magazines that publish content about the disease to get a paper written . A student has to study the available information thoroughly and analyze it before writing an HIV AIDS research paper. And this is not easy because students have lectures to attend and other assignments to complete while writing research papers.

Why Write an HIV Research Paper

Preparation for writing an hiv research paper, how to write a research paper on hiv, topics for hiv papers.

But, research alone is not enough. Learners should also be persuasive in their writing for their papers to stand out and earn them the top grades. Ideally, a learner should present ideas in a way that convinces the reader that they engaged in a thorough research process before composing the paper. If struggling to compose a strong HIV and AIDS research paper, this guide comprises relevant topics and tips that should guide you.

HIV/AIDS is a preventable disease. When implemented properly, prevention intervention can reduce the transmission of this disease. What’s more, people infected with HIV/AIDS can make behavioral changes and improve their health. Such changes can also reduce the risk of infecting others with the disease.

• When a student engages in research and then writes a paper on HIV AIDS, they learn such aspects of this disease. Ideally, this academic task equips the learner with the knowledge and information required to guide and help people avoid this disease. It also enables them to counsel those living with HIV to lead better lives without transmitting the disease to other people.
• A student will most likely be required to write a research paper about AIDS and HIV when pursuing medical or social science studies. That’s because they will most likely meet people living with the disease or at a higher risk of infection once they venture into the job market. As such, such people will play a significant role in increasing awareness of the disease once they start working. Some individuals are already working while pursuing their studies. Therefore, this assignment equips them with relevant knowledge that they can apply every day at their workplaces.

The reason you’re reading this article is probably that you’ve been assigned a research paper about HIV. However, you don’t know how to complete this task or even where to start. Although you may find a lot of information on this subject online, there are hardly any guides for writing a research paper about it.

To compose a great AIDS research paper, you need to prepare adequately. Here are the three steps to follow when preparing to write an HIV essay paper.

• Choose a topic : You’re supposed to write about HIV/AIDS. However, there are many aspects of this disease that you can write about. Therefore, start by selecting a topic for your research paper. For instance, you can write about the effects of HIV on specific demographics. You can also write about the changes the fight against HIV/AIDS has undergone over the years. Ideally, pick a topic you will be comfortable researching and writing about. Also, make sure that your topic is not too narrow or too broad. That’s because an extremely narrow topic will limit you when it comes to the information you can include in your paper. A broader topic will seem shallow because you won’t cover every aspect of it in your paper.
• Compose a thesis statement : A thesis statement for HIV paper should tell the audience what the paper is about. Your reader should know what to expect in the rest of the paper after reading it in the introduction. Therefore, come up with a clear thesis statement that captures the main theme or idea of your paper. You should compose a thesis statement after conducting preliminary research about your topic.
• Draft an outline : An HIV paper outline is the skeleton of the entire paper. It shows where the information gathered through research will appear in the paper. Ideally, an outline should help with the organization of your ideas and information in the research paper.

Once you’ve chosen a topic, composed a thesis statement, and outlined your paper, you can now proceed to actual writing.

When writing your research paper, focus on answering the questions that the audience might have after reading your topic. To do this, follow these steps when writing a research paper on HIV AIDS.

• Research your topic extensively : You can find many online sources, journals, books, and magazines with information about HIV/AIDS. Composing a great paper requires you to research your topic extensively. If you’re writing a concept paper on HIV AIDS, ensure that your message comes out. For instance, you can expound on the epidemiological landscape of the disease. This includes the challenges and history of HIV prevention. After research and learning all you can about the topic, analyze your information and then come up with the main points to present in your paper.
• Write the introduction : Start by introducing your topic to the audience. Tell them why you chose this particular topic and why it’s worth exploring. Your intro to a paper about HIV can also provide background information. For instance, you can provide statistics that show the impact of the disease on a specific demographic group. Use a relevant hook in the introduction to capture the audiences’ attention and make them want to read the rest of the paper. Also, include your thesis statement in the introduction. That way, your audience will know what your paper is about after reading the introduction. They also decide whether to read the entire paper or some of its sections.
• Write the body : The body of a research paper on AIDS is where you expound on your main points. For instance, if you want to write about HIV prevention, you can expound on the major prevention measures. Tell your readers what every prevention measure entails and how effective it is. You can include statistics to support your point. Present every point in its paragraph and support it with relevant information.
• Write the conclusion : Compose a conclusion for your AIDS paper by wrapping up your argument nicely. Remind the audience what you set out to do by restating your thesis statement and then show them how you’ve accomplished your mission. You can also leave the audience with something to think about or suggest ideas for further research on your topic.

Writing your paper will be relatively easy if you follow these steps. However, you should pick a good title for AIDS research paper because this will dictate the direction of your research and writing process.

As hinted, choosing the right topic is very crucial because the title of your paper will influence the direction of your research and writing process. HIV/AIDS is a broad subject with many health research topics that learners can research and write about. Here are sample topics to consider when writing a paper about HIV/AIDS.

• How the AIDS virus affects the human immune systems
• How HIV/AIDS compares to most diseases affecting the human DNA
• The most effective methods for curbing the spread of HIV
• The origin of the AIDS pandemic
• Is AIDS a pandemic or epidemic disease?
• Countries with the highest cases of HIV/AIDS and why
• Common myths about HIV/AIDS
• Effects of stigmatization of the people living with HIV/AIDS
• How governments help HIV/AIDS patients
• Why pregnant women undergo HIV/AIDS testing
• How ignorance contributes to the stigmatization of HIV/AIDS patients
• Strides made by medical researchers towards the prevention and possible cure of HIV/AIDS
• How misconception of HIV patients affect their lives
• Common stereotypes about HIV patients in movies
• Factors that accelerate the spread of HIV in developing countries
• How a person’s sexual behavior influence their risk of contracting HIV
• How the struggles of men and women with HIV compare
• Why the world has a hard time preventing the spread of HIV/AIDS among teenagers
• HIV prevention measures- How they compare between the UK and the US
• Common opportunistic illnesses among people with HIV/AIDs

Whether you choose to write an HIV reflection paper or HIV AIDS reaction paper, take your time to conduct extensive research and analyze your information. Also, list down all your sources when researching your topic because you will need them when composing the reference section of the paper. If possible, include in-text citations to help your readers engage in further reading. This will help readers that are interested in a specific aspect of your topic. Also, take your time to research your topic and analyze information before composing your HIV research paper thesis. That way, you will come up with a statement that will reflect what your paper will cover.

264 HIV Essay Topic Ideas & Examples

🏆 best hiv topic ideas & essay examples, 👍 good essay topics on hiv, 📑 interesting topics to write about hiv, ✅ good research topics about hiv, ⭐ simple & easy hiv essay titles, 📌 most interesting hiv topics to write about, ❓ hiv research questions.

• Prevention and Treatment of HIV/AIDS Gates Foundation The main objective of the Gates Foundation is “to reduce the incidence of HIV infection and extend the lives of people living with HIV”.
• The HIV/AIDS Epidemic in the Movie “And the Band Played On” In particular, they knew that many of the patients had sexual intercourse with one another, but they could not explain why this disease was widespread in the gay community. We will write a custom essay specifically for you by our professional experts 808 writers online Learn More
• HIV/AIDS in Papua New Guinea Even though the disease was first noticed in the earlier years of the 1980s, it was news to the country of Papua New Guinea till in the year 1987 when the first case of AIDS […]
• HIV and AIDS in Adolescents The teenagers in America and the world are a group that is constantly at risk of infection with the Human-Immunodeficiency-Virus and developing the Acquired-Immune-Deficiency-Syndrome, the disease condition that eventually results; this is stemming mainly from […]
• The International Problem of HIV/AIDS in Modern World In addition, the effects of HIV/AIDS today are not only confined to the families and individuals infected, but also involve the political, economic, and social factors of the country and people in the country.
• Epidemiologic Triangle Elements Applied to HIV The epidemiologic triangle can be extremely beneficial in this perspective, because it “is a model for explaining the organism causing the disease and the conditions that allow it to reproduce and spread”. Anyway, the spread […]
• AIDS Discrimination in “Philadelphia” (1993) by Jonathan Demme “Philadelphia” is the film that appeared on the screens at the end of the 20th century. He is a lawyer, who copes with his duties easily and is known as one of the best professionals.
• Ethical Issues on HIV/AIDS The issues to be discussed include ethical issues related to research and counseling for AIDS patients, discrimination, and intentional transmission of the disease and the protection of vulnerable groups in the society.
• HIV/AIDS Education’ Importance for Young People Due to the impact of this challenge in many countries, better education system that informs the youth and new generation is essential in informing the youths on the safety behaviors that can help reduce the […]
• HIV in South Africa This negative side of the warfare led to the re-interpretation of human security on the onset of the Cold War that ushered in the second phase of the human security approach.
• HIV Testing of High School Seniors Should Not Be a Mandatory Requirement for Graduation Still if a policy like mandatory HIV screening of students is formulated by the governing body of the University it is the indication of a serious lack of proper understanding of HIV/AIDS and the rights […]
• HIV-AIDS and Male Circumcision: The Cases of Kenya and Sri Lanka In India, religion and culture have been identified as impediments to the fight and prevention of HIV-AIDS. Religion as the main basis of culture has resulted in the entrenchment of the ban on circumcision to […]
• Anglo American Plc’s HIV/AIDS Strategy The stakeholders include the South African government, the Anglo American employees, the populations of surrounding communities, families of employees, the Global Council on HIV/AIDS, The National Union of Mineworkers, pharmaceutical companies and other multinational companies […]
• HIV/AIDS in Africa and The PEN-3 Model In most communities in Africa, the prevention of HIV/AIDS lies within the cultural practices. In conclusion, the fight against HIV/AIDS in Africa should lie parallel with the eradication of cultural practices, which hinder promotion of […]
• AIDS/HIV: Description of the Disease This is the very reason why many who have acquired HIV or AIDS result to an eventual death because of the lack of immune system that protects them from acquiring other forms of illnesses.
• HIV/AIDS Stigma in Tanzania The education sector is also affected due to the rise in the number of orphans who at times are forced to drop out of school owing to lack of parental care.
• Thailand Issues: Environment, Child Prostitution, and HIV/AIDS The intensification of child prostitution is largely associated with the growing industry in Thailand, the relegated position of women in the Thai society due to Thai Buddhism and the culture of recreational sex.
• HIV-AIDS in News Reports and Literature The report further shows that the use of ART has led to a reduction in the total cost of managing HIV-related cases annually in low and middle-income countries.
• Microbial-Environmental Interactions in HIV & AIDS The virus manifests in two subtypes, HIV-1 and HIV-2, and the severity of infection depends on the type of viral attack.
• HIV and AIDS Prevalence in South Africa According to Africa Science Focus, despite effective HIV/AIDS treatments available around the world, there is a distinct inequality in the ability of South Africa to access them. Before listening to the podcast, I knew that […]
• Human Immunodeficiency Virus and AIDS in Women HIV and AIDS are global health problems affecting women disproportionately due to cultural beliefs and worldviews. Biological variations also contribute to the spread of HIV and AIDS among women due to peculiarities of their body […]
• Addressing the Issue of the HIV Epidemic in the US It aims to end the HIV epidemic in the country by utilizing the latest scientific advancements in diagnosis, treatment, and prevention.
• Living With HIV: Stigma and Discrimination The mental health and emotional well-being of the population living with this virus are affected due to the humiliation and judgment they face from their fellows around them.
• Recent Advancements in HIV Treatment An example of a recent advancement is the approval of Cabenuva, an injectable HIV therapy reducing the need for daily medication intake.
• Nursing: HIV Among Queer (LGBT) Community A combinatory program is required to reduce the rates of HIV transmission, improve the prevention techniques against the virus and ensure the early-stage diagnosis procedures are as effective as possible.
• HIV-Positive Women’s Mental Health Problems Peer review implies the submission of the article describing the details of the research process and the design to a journal that then sends this article to the professionals working in the same field, who […]
• The HIV Vaccine: Discontinuation of Trials Therefore, the primary benefit of this study is that people could get immune to the HIV infection, provided the vaccine worked.
• The Stigma of People Living With HIV and AIDS Consequently, in this case, it is recommended to pay special attention to the development and implementation of policies to combat HIV/AIDS stigmatization from the point of view of taking into account the interests of older […]
• Aspects of Stop AIDS Delaware Initiative The four that are incredibly essential to their own lives as well as to a wider community include emotional resilience, communication skills, medical knowledge of the condition, and empathy.
• Stigma and Psychological Distress in HIV Caregivers The inclusion criteria of the participants in the study were if they had a confirmed HIV diagnosis. This study’s findings are similar to the findings in “Depression, anxiety, stress, and stigma in informal caregivers of […]
• Math: Aspects of HIV Modeling The indicator of the fit of the constructed model to the data set is the parameter R2, the coefficient of determination.
• Ethical and Legal Issues With the Disclosure of HIV Status of Healthcare Workers The first glance at the situation compels one to immediately support the idea that healthcare professionals should disclose their HIV status since the alternative scenario would pose a significant health risk to a patient.
• Adherence to Antiretroviral Therapy Among HIV People The abstract provides a concise summary of the background of the research, aims, methodology, results, and conclusions to help the audience understand the without reading the entire report.
• HIV Infection: Diagnosing and Testing Therefore, a comprehensive approach to clarifying the diagnosis, using a synthesis of scientifically based and subjective aspects of the course of the disease. The purpose of this study is to determine a comprehensive approach to […]
• HIV-AIDS Prevention & Advocacy Through Legislation Despite the existing programs to promote HIV/AIDS prevention among the population and criminalization of the failure to disclose HIV status prior to sexual intercourse, the Florida state legislature does not obtain any mandatory outreach and […]
• Increasing Public Awareness of HIV Infection The HIV denialism movement, which emerged almost immediately after the discovery of the disease and its identification as the cause of AIDS, actively promotes anti-scientific hypotheses about the absence of both the virus itself and […]
• Stories of People Battling HIV-AIDs She always ensures that supportive communication is at the center of her engagement with the children and shows acceptance and respect to improve her relationship with them.
• Counseling Clients With HIV-AIDS Thus, the central recommendation for human service professionals counseling clients with HIV/AIDS is to allow time for the shock of the news to sink.
• HIV Subtype Diversity Worldwide HIV is a severe global health issue because almost 40 million people were infected in 2017. That is why it is not surprising that Australians also suffer from this health problem.
• Los Angeles: Community Strategic Plan For STD and HIV Reduction Thus, one of the main concerns is the risk of transmission of both STDs and HIV due to the crisis of homelessness and loneliness in Los Angeles Country.
• Vulnerable Population: HIV-AIDS The latest statistics identify HIV/AIDS as a major medical problem affecting the health sector. The disease currently affects over one million citizens.
• African American Women With HIV: HIV Treatment Compliance The sampling strategy that will be used in the study is simple random sampling. This strategy will be appropriate because it is likely that the sample will be representative of the general population, for any […]
• HIV, STI as a Public Health Issue In light of the fact that the HIV/STI development levels remain rather high among the target population, the necessity to educate young people about the threats of HIV/STI, as well as the methods of avoiding […]
• Health Interventions in the AIDS Epidemic This development has created the need for introducing the social-ecological model in curbing the increased rates of HIV infection in some communities. This paper identifies income and stigma as the main social factors that affect […]
• Changes in the Research on AIDS Some of the current researches on this disease include treatment of the disease, the content of Aids protein and the preventive modes.
• The Most Effective Methods of Preventing the Spread of HIV Recent statistics show that in the United States the number of people living with HIV and AIDS is higher among men than women.
• Segregation of HIV-Positive Prisoners The biggest debate on segregation of HIV-positive prisoners surrounds the ethical impact it renders to the inmates. The proponents of segregation of HIV-positive prisoners believe that segregation protects prisoners and the correctional staff from catching […]
• The Problem of Homeless Youths With HIV-AIDS Studies carried out in the city of New York in 2008 showed that 21 percent of homeless youth males and 24 percent of homeless female youths had “more than 100 lifetime partners”. 5 percent of […]
• Country Health Policy Proposal on Improving HIV-AIDS Outcomes in South Africa One of the significant public health problems facing the South African public health system is the high prevalence of HIV/AIDs. Inefficiency of the public health system contributes significantly to the HIV burden in South Africa.
• HIV/AIDS and International Health Community Over the years, the level of people’s awareness about the notion of HIV/AIDS has increased dramatically, yet the health condition itself remains frowned upon and stigmatized by the global community.
• AIDS, Then and Now This view spread to the U.S.culture at large and contributed to an exaggerated representation of the disease as a “gay plague” in the media.
• Film “The Silent Partner: HIV in Marriage” In a region whose fight against HIV is slowed by a lack of awareness, the film shows how traditional ways of fighting the pandemic fail to serve the needs of married women.
• Communicable Disease Health Education Tool: HIV, AIDS The Human Immunodeficiency Virus (HIV) is a contagious that causes a condition known as the Acquired Immune Deficiency Syndrome (AIDS).
• The HIV/AIDS Situation in India Most of the initial cases had occurred through heterosexual sex; but at the end of the 1980s, a rapid spread of HIV was observed among injecting drug users in Manipur, Mizoram and Nagaland. An explosion […]
• HIV, Health & Rights – Sustaining Community Action In general, the strategies are useful since they focus on the existing challenges and address the target population. In conclusion, one can state that the strategic drivers have been successfully developed into the four directional […]
• Saudi Student Nurses’ Perception of Their Educational Preparation for HIV/AIDS Patient Care In this research, the review will explore the current knowledge and literature regarding the level of comfort of nursing student’s on educational program preparation for the care of people living with HIV/AIDS in Saudi Arabia.
• HIV in Saudi Arabian Children Analysis For a long time, this society has considered those who are suffering from HIV as adulterous and are not living according to the teachings of the Quran.
• Problem of HIV in Saudi Arabian Children Although the rate of HIV infection still remains low when compared to the world’s average, the number has been on the rise over the past five years.
• HIV and AIDS as a Chronic Disease: The Unique Contributions of Nursing Through Philosophical, Theoretical, and Historical Perspectives In most societies across the world, the responsibility of caring for the sick in the community feel on the family and the entire society.
• The Historical and Current Role of Stigma in the Provision of HIV and AIDS Care: The Context of Ghana The paper describes the historical and current role of stigma in the provision and care of people living with HIV and AIDS in the context of Ghana.
• Men Issues With HIV/AIDS in Miami Various men’s issues and social well-being have contributed to the increased rate of infection among men in Miami and Florida. In conclusion, the rate of HIV/AIDS infection in Miami is higher among men than among […]
• From Exceptional to Chronic Illness: New Challenges in HIV Prevention in the UK The current paper is an attempt to analyze the shift in the perception of HIV from an exception to a chronic illness and the new challenges experienced in HIV prevention in the UK.
• Researching HIV, AIDS and Social Justice Disney claims that poverty and social injustice lead to the spread of HIV/AIDS among underprivileged people in all countries. The disease was a kind of stigma and infected people were subjected to discrimination and alienation.
• The Threat of HIV, AIDS and the Means to Avoid It Taking into account the results of the case study conducted by Cornish and Ghosh, instances of people in India becoming infected with the HIV virus have increased recently, which is given as a reason for […]
• The Combivir Medication in HIV, AIDS Treatment Hence by blocking the enzyme the rate of virus multiplication is reduced and consequently the amount of HIV cells in the blood is reduced.
• Natural HIV Control by Bruce Walker The ability of the immune system of individuals to fight HIV infection depends on T cells and not by how many T cells are produced. The article is important in that it shows the role […]
• The Policy Topic on the Impact of HIV/AIDS Pandemic in the USA This paper will discuss the policy topic on the impact of the HIV/AIDS pandemic in the United States and the rest of the world.
• Circumcision of Male Infants as a Way to Combat the HIV Therefore, by circumcising all the men, the rate of heterosexual infections in Australia will reduce considerably as circumcised men are lesser prone to HIV infections than uncircumcised ones.
• Genco Company: A Distribution of HIV-AIDS Drugs in Malaysia The management of Genco Company should be keen on setting out the date of registration because it helps to determine the period, which the business will be legal to operate in the country.
• HIV From a Social Sciences Perspective In the US, the disease was initially associated with gays only but in the recent past, it is has been claiming many lives in the country and other parts of the world. The first social […]
• Microbiological View of HIV Epidemic and Possibility of Discovering Its Cure The glycoprotein facilitates attachment and fusion of the virus to human cell membrane. In Golgi complex it is cleaved by protease and proceased in to human immunodeficiency virus and released.
• HIV (Human Immunodeficiency Virus) Prevention In so doing, they ignore the importance of the community in the prevention of HIV transmission. HIV prevention strategies that focus on the social drivers of HIV transmission are usually very effective.
• HIV/AIDS Pandemic Facing the Female Global Population The questions that arise are; what factors are contributing to the prevalence, who are the most affected and what are the actions taken to mitigate the HIV/AIDS epidemic?
• HIV Transmission From Homosexual Men Receiving Cure The study reaches the following conclusions: In general, male partners to MSM receiving treatment are at risk of contracting HIV virus although the risk is relative to condom use as well as the last time […]
• Depressive Symptoms and HIV Disease Relationship Moreover, the study also noted that it was imperative to identify and treat causes of physical symptoms while self-esteem and emotional support for HIV-positive pregnant women required strengthening in Thailand.
• Hepatitis C and HIV Among Intravenous Drug Users In relation to this health issue of HIV and HCV, the community health nurse has the responsibility of promoting health among intravenous drug users.
• Addressing the Needs of HIV Patients According to the latest report published on the subject matter, the therapy provided to the patients in question implies that the family members should take an active part in the process of managing the disorder […]
• Decreasing Inflammation in People With HIV: The Efficiency of Low-Dose Methotrexate The principal objective of the research is to obtain a numerical estimate of the issue and the reaction of respondents towards it.
• HIV Pandemic in Africa and the United States However, there is no epidemic of AIDS in the United States due to appropriate measures conducted by the government including the prohibition of the polygamy and anti-drug policy. Additionally, authors regard the role of the […]
• Communicable Disease Control Strategies for AIDS Governments should consider AIDS as a health priority, among the strategies to control the spread of disease are ensuring that public and private sectors are sharing AIDS’ responsibility, provision of enough resources to research on […]
• Guidelines on HIV and Infant Feeding The objective of this guideline was to find ways through which HIV-positive mothers can protect their HIV-free children from a possible infection.
• People Infected With HIV in India The proposed research aims to highlight the particular factors that led to a decrease in the number of people infected with HIV in India.
• Pneumonia Infection & Risk of Mortality in HIV-Infected Children The topic is quite interesting because only a few studies have attempted to focus on the role of HIV infection on the rates of mortality and morbidity rates in pneumonia infections. It is the first […]
• HIV Rates and Infant Mortality: US, UK and Kenya The purpose of this paper is to compare the HIV rates and infant mortality cases of the United States with the situation in a developed country such as the United Kingdom) and a developing nation […]
• Disclosure of a Physician’s HIV Status The addition of another corpus that needs the disclosure of HIV/AIDS status to partners is as important as it is harmful if done without prior consent.
• AIDS: The Legal Rights and Responsibilities of Employees and Patients It is the responsibility of employees to adhere to adjusted schedules and to maintain high productivity and efficiency. Employees also have a right to assess information on HIV and AIDS in the workplace.
• Late Phase of HIV Type 1 Replication The Late Phase of HIV type 1 replication involves the assembly of Gag proteins with the plasma membrane of hematopoietic cells.
• Baby With HIV Is Deemed Cured After reading the article, the first question I asked myself was whether it is possible for a baby with HIV to be cured without medication.
• Routes of HIV Transmission Based on the NACO annual report, it can be seen that the primary drivers of the HIV epidemic in India are commercial female sex workers, drug use and unprotected sex between homosexuals and heterosexuals.
• Health Services Research: AIDS-Related Stigma The information obtained from the analysis of the research findings are used by the healthcare organizations and policy makers to improve on the delivery of quality healthcare services to the people.
• HIV Intervention in Gay Community The AIDS scourge is at the center of this study because this paper seeks to address AIDS as a special health concern affecting the gay community in the Montrose area, with a clear aim of […]
• Risks for HIV&AIDS in Juvenile Detention The participants in this study willingly shared their perceptions and experience of risk for HIV/AIDS within the context of their social and ecological environments and, in so doing, embodied other models of interaction and behavior […]
• The Impact of HIV and AIDS Epidemic on Women In the anatomy while having intercourse the vagina is very susceptible to tears and irritations when engaging in sex and thus with the tears and the irritations the exposed flesh offers a good penetrating surface […]
• The Impact of Social Determinants of Health in the HIV-AIDS Efforts have been made to contain the pandemic but in vain, and that is why researchers are concentrating on the social determinants of health in the context of HIV/AIDS.
• The Social Environments and the Effectiveness of Youth HIV Prevention It is saddening that most of the youth view sex education negatively since their elders have socialized them to view it as a curse.
• Combining Efforts to Combat HIV and AIDS The difference in health care systems and standards of health care resources available in different parts of the world, greatly affect the course of the disease in individuals and groups.
• Research Into the Causes of HIV Though HIV is still incurable in modern days, one of the problems that people in slow developing countries face is high death rate from HIV due to the lack of funds for purchasing effective medication […]
• The Problem of HIV & AIDS in Spain: The Leading Rate of Infection in Europe Considering the fact that Spain has the leading number of the homosexual in Europe, the rate of the infections in this group stands at 10%.
• HIV and People Who Use Drugs: Cases of Infection Caused by Injection Drug Use The existing condition of the epidemic in a certain region can be termed as low-level, concentrated, or generalized depending on the prevalence levels of the virus in the specified demographic.
• Concepts of Culture and Disease Paper: AIDS However, in general, African governments and non-governmental organizations with the help of the United Nations Department of AIDS, UNAids, continue to educate Africans on the spread, symptoms, and other AIDS factors. In sub-Saharan Africa, numerous […]
• AIDS and Its Trends: An Infectious Disease That Causes the Vulnerability of the Human Internal System These facts address the query of the author having the valid experience to make writings regarding the Disease, it is clear that he had first-hand experiences. The disease is manageable with the use of drugs […]
• Effects of HIV and AIDS on Young Children and Women The hypothesis of this study is to establish the prevalence of HIV and AIDS on the general population this is with particular attention to the young children and the women who are more vulnerable.
• HIV Counseling and Testing: Lifetime Treatment Program Some of the possible intervention that can be adopted by the clinicians in order to improve adherence include the encouragement of the patients to be in contact with people of their age who will encourage […]
• Epidemiological Analysis of the Acquired Immune Deficiency Syndrome (AIDS) The virus is found in most of the body fluids of the infected person; and this is the main route of infections.
• Drugs for the Treatment of HIV Infection: Over 30 Antiretroviral Drugs to Counter the Effects of the Deadly AIDS Virus By the latest study, the Food and Drug Administration has approved 30 antiretroviral drugs to counter the effects of the deadly AIDS virus According to the National Institute of Allergy and Infectious Diseases, the drugs, […]
• Health Care Management: HIV and AIDS Prevention and Treatment To define the measurement system, and define the failure or success of HIV/AIDS treatment it is necessary to give the image of the situation in general.
• HIV, AIDS Health Determinants in Africa: The Research and Development in Curative and Preventive Medicare Emphasis was laid on the research and development in curative and preventive Medicare so that the members of the society lived a healthy life. This is compared to a total of between 130,000 and 180,000 […]
• HIV Crisis in Africa: Review of Major Public Health Concerns on the Continent The paper will examine the issue of HIV/AIDS in Africa, focusing on the effects of the disease, procedures of its containment, and the prevention tactics used by the African public.
• The Spread of HIV and AIDS in Prisons: Causes and Measures of Control Other causes of the spread of the disease include overcrowding and lack of education on the danger of the virus. At-risk individuals need to be sensitized about the devastating consequences of this virus and the […]
• ART HIV Medicine Saves Lives: Maintains Functions of the Immune System and Prevents Opportunistic Infections The goal of the essay is to increase the level of awareness of readers on the importance of ART. A brief overview of HIV treatment programs should also be included in the essay to support […]
• HIV: Overview of the Clinical Manifestations of Infection and Symptoms and Known Cases of Complete Cure The information includes detailed information about the molecular structure of the virus, the form of the genome, and the mechanism of self-reproduction within a targeting cell.
• Faith-Based Organization Services as the Best Means to Prevent HIV and AIDS in Southern Cameroons The HIV/AIDS issue was complicated by the fact that at the moment of this research, there was no cure and the only way of addressing the infection spread was through prevention and ensuring that people […]
• An Enzyme-Linked Immunosorbent Assay and Drug Treatment for HIV and AIDS It is also vital to stress that non-adherence leads to the return of the symptoms and the development of HIV-related diseases that could lead to death.
• HIV & AIDS Diagnosis and Treatment Measures After decades of its first appearance, the human immunodeficiency virus, which causes AIDS at a more severe stage, continues to be a major threat to human health and searches for developments in diagnosis and treatment.
• Breast Cancer and AIDS: Significant Issues in the United States in the Late 20th Century Thus, the given paper is going to explain why these activists challenged regulatory and scientific authorities and what they demanded. That is why the enthusiasts challenged their practices and made specific demands to improve the […]
• The Effect of HIV Treatment on Individuals and Contributing to a Longer Life of the Patients As a result, better treatment of the illnesses globally and especially in Africa has contributed to a longer life expectancy of the patients.
• Male Circumcision for HIV Prevention in South Africa The primary purpose of this study is to determine the cost-effectiveness of the use of circumcision and if this practice is appropriate.
• Misinform Partner’s HIV-AIDS Status: How to Prevent From Being Misinformed However, I believe that the key to avoiding the issue of the HIV growing epidemic does not lie in the doctor’s duty to anonymously inform one’s sexual partners.
• The Issue of HIV-AIDS-Positive Status Disclosure Whereas at the beginning of the epidemic, the therapists felt it was their duty to inform the patient’s surroundings of the issue, the introduction of the HIV/AIDS Confidentiality Act turned this duty into a forthright […]
• Global Health Issue Analysis: HIV – A Relatively New Disease Rapid detection and treatment are crucial to limit the spread of HIV and limit the patient’s effects. As the frequency and intensity of symptoms vary from person to person, testing is the only clear way […]
• High Risk of HIV Among Injection Drug Users The aim of this Health Promotion Plan is to improve the situation with infection diseases spreading among the injection drug users due to the social importance of this problem and the high level of mortality […]
• Childhood Sexual Abuse and HIV Risk in San Salvador Still, the women interviewed presented a peculiar layer of the society that made it possible to understand the clear connection of the CSA to HIV/AIDS and drug addictions.
• New Directions and Strategies for Current and Future Research in HIV The authors therefore are in agreement that future research paradigms focusing on HIV should lay much focus on developing an efficacious vaccine to curtail further spread of the virus.
• Health and Health Policy of HIV and AIDS: Physical and Psychological Wellbeing Health is defined and understood as the state of full physical and psychological wellbeing, and not just the absence of diseases in the body, while a health policy is the plans, strategies and actions undertaken […]
• Bubonic Plague and AIDS: Differences and Similarities Transmission of the diseases is also another area that generated debate in the entire course of The Plague and during the initial stages of AIDS.
• Pricing AIDS Drugs Sold to Developing Countries The majority of the world’s HIV/AIDS cases are in Africa particularly the sub-Saharan and many of the infected have been faced with a huge challenge to live a normal life due to limitations in access […]
• Does Black America Need White Support in Order to Combat HIV, AIDS Epidemic? The economic instability, the lack of education and improper health care facilities all attribute to the spread of the epidemic in the black community which is set to rise in the coming years.
• Women With AIDS in Africa: Treatment Possibilities Starting with the economical issues, the countries of Africa are the countries of the third world and the economy is very weak in the area.
• The Relationship Between the High Rate of Urbanization in Africa and AIDS Spread This movement results in to increase in the number of people in the towns and cities in a particular year. The increased social interaction of people in towns has led to increased HIV/AIDS infections in […]
• Language and Stigmatization: Cancer, HIV, and AIDS Much has been written concerning the alarming spread and effects of HIV/AIDS in the society and the effects of cancer and the position of its victims and how to care for them.
• The Human and Economic Effects of AIDS on the United States The social impact of HIV has been well documented and widely distributed which has served to educate the public and acted to stem the tide of the epidemic.
• Workplace Stereotypes About People With HIV: Business Ethics After analyzing the every angel of the case, it can be said that this is the picture of the stereotyping prejudice of people with AIDS.
• Capitalism and Industrialization as a Cause of AIDS Spread Population growth rates are the highest in most of Asia, Africa, and Latin America due to the high degree of fertility and the dramatic decrease in mortality following World War II.
• The Pharmaceutical Industry Faces AIDS in Africa Food insecurity in these countries has to lead to the quick progression of patients to full brown AIDS and completely worsened the immunity of the patients.
• HIV, AIDS and the Social Environment The obvious place to start is to find out the sociological impact of HIV/AIDS with regards to the infected person. Thus, there is a tendency to concentrate on the scientific aspect of the disease as […]
• African Gold: Ethics and AIDS in the Workplace The issue that is troubling the management of the organization in the case, African Gold is that of the costs, medical costs and disability programs as a result of the rising workforce succumbing to the […]
• Center for Disease Control and HIV Prevention Goals The first short-term mission of the CDC Preventions is to increase the percentage of those HIV-affected people who indulge in such activities which alleviates the risks or dangers of HIV transmission.
• AIDS Infection in Europe Statistics: A National Disaster in Many Countries Most of these young men and women that engage in this business are end up being infected with HIV virus since they do not have the power to negotiate for safe sex and especially the […]
• Rational System of HIV Disclosure Laws Since the start of HIV pandemic, the humanity aimed to regulate and minimize the spread of the infection. The people, who became the victims, as they were unaware of the danger of the infection, finally […]
• World AIDS Day Celebration: Increasing the Awareness of the People About the Disease The World AIDS Day is not just celebrated in the United States, Europe, or Asia, it is observed all over the world because the disease does not only affect this part of the globe, but […]
• Public Policy Development. AIDS.gov Benefit Types CDC is a premier public health agency which undertakes the control and prevention of AIDS in US, and their mission is to promote health and quality of life.
• Public Policy. Eligibility Rules Used by AIDS.gov There are no restrictions that prohibit the tailoring of health care programs by clients and using various services and providers that are eligible for meeting the health care needs of individuals.
• HIV/AIDS and Orphans in Sub-Saharan Africa On the choice of orphans in sub-Saharan Africa as the topic for this research, it aims at addressing the cause of overwhelming numbers of orphans in the region and how this impacts society.
• Social Networks of People Living With HIV and AIDS The purpose of the study was to compare the social networks of younger patients with the older ones. The convoy theory of social support lent credence to the research.
• Changes in Prostitution and AIDS Epidemic in Thailand This provided information on commercial sex trends such as the types of CSEs in existence, the number of sex workers, and the price of sex. However, the decline in the number of sex workers was […]
• How AIDS.gov Fund Its Programs to Respond to the Impact of the Epidemic on Ethnic and Minority Populations Transportation costs to go to the clinic and lost wages should be accounted for and records kept acting as evidence of how the funds were used.
• The Pharmaceutical Industry and the AIDS Crisis in Developing Countries One of the reasons of this difference is that excise and custom duties that are responsible for the unaffordable prices of medicines have been avoided by the developed countries by the creation of pharmaceutical industries, […]
• Advancements in AIDS Research: A Potential Advancement in the Attempt to Cure HIV Infection After HIV’s genetic code is altered from a single thread to a double-strand by the reverse transcriptase enzyme, it gets included in the genetic code of the infected cell.
• Ethics of Leukemia Treatment With Disabled HIV Cells In recent years, the medical community has pondered the radically new approach to cancer treatment, which is isolating and collecting T-cells from the patient.
• AIDS: Emergence Factors of Infectious Disease Emerging diseases refer to the newly identified pathogens that have been recognized in the past few decades that lead to a new manifestation of diseases.
• AIDS and Its Impact on Humankind: The Leading Killer Disease in the World From these statistics, it is easy to deduce the effect of the disease of humankind. At the international level, more and more funds have been committed to the treatment of AIDS.
• AIDS in a Different Culture Review: Cultural Differences, Prejudice, and Racism Now, gay youth and men face the possibility of HIV infection in the course of sexual relationships. The pejorative view of gay men prevalent in some black and Hispanic communities can inhibit they are coming […]
• Lewis’ Race Against Time: Curbing HIV&AIDS in Africa Lewis points out that, “HIV/AIDS has sabotaged all of the socioeconomic indices, and the continued damaging western policies in trade and aid and debt, serve to drive the nails into the coffins”.
• Community Health. HIV/AIDS Prevention for the 50+ The specificity of the paper is that it relates the issue of HIV prevention for the people over 50. It is necessary to mention, that: 10% of all AIDS cases in the USA are people […]
• Microbiology. AIDS Vaccine Studies: Different Developments Strategy So far there is no practical hope that ongoing AIDS vaccine development will produce tangible results, According to one of the leading AIDS vaccine expert Mr. Clinical trials will have to continue as they will […]
• Medical Anthropology. HIV&AIDS Preventive Measures Since the detection of the first case of HIV in India, the government introduced both surveillance and preventative plans to reduce the risk of the disease spread.
• Drug Treatments for HIV/AIDS To lower the complacency of people to HIV/AIDS and change the perceptions about the condition for individuals with and without HIV/AIDS, health care professionals should focus on such aspects as safety, responsibility, and stigma.
• Descriptive and Analytical Epidemiology: Tuberculosis and HIV The establishment of trends in the epidemic process for the rapid introduction of adjustments helps optimize preventive and anti-epidemic measures alongside the evaluation of the effectiveness of the activities.
• AIDS and Its Related Aspects The report aims to show that clinicians and nurses should discuss AIDS and associated risks with their patients to enhance individuals’ health outcomes and eliminate the prevalence of the disease.
• Anti-HIV Nonprofit’s Organizational Design Particularly, three areas of concern are of the primary interest: the design and functional characteristics of NGOs, the problem of HIV in the context of NGOs, and differences between organic and mechanistic organizational structures.
• HIV and AIDS: Legal and Ethical Conduct
• OraQuick Home HIV Test and Its Pros & Cons
• Female HIV-Positive Patients’ Medication Adherence
• Immunology and Virology of HIV Infection
• Mandatory HIV Screening: Ethical Issues
• Spreading and Dying From AIDS and the Increasing Spread of the Disease
• Health Fraud: HIV/AIDS and Sexual Enhancement Scams
• HIV and AIDS Early History and Risks
• HIV Prevention Programs in Africa
• HIV and AIDS Infection Levels and Their Social Effects
• HIV Prevalence Among American Queer Communities
• HIV Testing Among African American Women
• HIV Rates Among African American Women
• HIV Prevention Policy Development for Chicago
• HIV Prevention Among Young Adults in Chicago
• Techniques for Helping Women With HIV
• Group Policy Regarding the HIV/AIDS Transmission Issue
• Pharmacology: HIV Drug Resistance
• HIV Prevention in Youth: Public Health Campaign
• HIV/AIDS as a Long-Wave Event in Politics
• Act Up Movement for Surviving HIV/AIDS Plague
• HIV/AIDS Activism in “How to Survive a Plague”
• HIV/AIDS Prevention by Anti-Retroviral Drugs
• The Impact of AIDS and Reasons Behind the Outbreak
• HIV/AIDS Policies in India and Antropological Study
• AIDS in New York in “How to Survive a Plague” Film
• ”The Cure for AIDS” by Apoorva Mandavilli and Various Ethical Issues
• Qatari Laws: HIV/AIDS Visitors, Pets, Dressing Code
• Legal Ethics, Patients’ Rights, and HIV/AIDS
• HIV/AIDS as a Communicable Disease
• Ancillary Services for HIV/AIDS Patients
• HIV/AIDS Patients: Legal Ethics and Patient Rights
• Medicine: HIV/ AIDS Campaign Slogan
• Medicine: HIV/AIDS as the Key Threat for the Kenyan Population
• HIV and AIDS in Kenya
• HIV/AIDS in Kenya: Evaluation Plan
• Health Promotion Program HIV/AIDS in Kenya
• HIV Among Adolescents – Treatment and Prevention
• HIV/AIDS Definition, Prevention and Treatment
• Medical Issues: HIV in the U.S.
• 5 Years Strategic Plan for HIV Prevention in Swaziland
• HIV and AIDS Prevention Among the Youth in Asia
• STD/HIV Health Promotion Evaluation Plan
• HIV and AIDS: an Evolving Global Response
• HIV Epidemic in Enrique’s Native Country
• AIDS: From the Perspective of Sociology
• Critical Analysis of Avahan – the India AIDS Initiative
• HIV/AIDS by Allan Whiteside
• The Rate of Smoking Among HIV Positive Cases.
• Critical Review of Chapter 5 and 6 of the Book HIV/AIDS
• AIDS Combating in the 21st Century: Issues and Challenges
• HIV/AIDS in the UK
• History of Treatment the HIV/AIDS
• Pathology of HIV and AIDS
• How the AIDS Epidemic Has Affected the World on a Political, Social, Economical Way
• The HIV and AIDS Problem Between Educated and Non-Educated Children in Uganda
• Implementation of AIDS Control Policies in Australia and South Africa
• HIV/AIDS Among African Americans
• AIDS: The Guilt and Failure of the West in a Spread of the Disease
• AIDS as an Epidemic of Signification: A Globally Potential Threat
• Key Drivers of HIV/AIDS in Sub Saharan Africa and in San Francisco
• Key Drivers of HIV and AIDS in Sub-Saharan Africa and in San Francisco and Church’s Response to the AIDS Pandemic
• Drivers of HIV and AIDS in Sub-Saharan Africa and San Francisco
• Impact of HIV/AIDS on Microeconomics
• Why Lack of Awareness Leads to the Spread of HIV/AIDS in New York Prisons
• Theory, Methodology and Human Development: HIV/AIDS and Education in African Countries
• Vital Signs: HIV Testing and Diagnosis Among Adults – United States, 2001-2009
• Community HIV/AIDS Mobilization Project (CHAMP)
• Communicable Diseases: HIV and AIDS
• Why HIV/AIDS Crises Are High in African-American Community
• A Project on Establishment of Jousing Flats Voluntary Counselling and Testing Centers in Njoro Area to Reduce Prevalence of HIV/AIDS and Provide Nutritional Support Among the Youths Aged Between 16-35 Years
• HIV/AIDS Issues in African Women
• AIDS in Lesotho, Africa: The Highest Prevalence Rate of HIV Infections in the World
• Prevention of HIV/AIDS in Rural Ethiopia: Identifying Risks
• Is Being HIV Positive a Disability?
• Why Does the Immune System Weaken With HIV Infection?
• What Is the Main Cause of HIV?
• How Does HIV Gain Entry Into the Cells It Attacks?
• What Can Gamma Delta T Cells Contribute to an HIV Cure?
• What Are the 4 Stages of HIV Infection?
• What Are the 5 Symptoms of HIV?
• Does the HIV Virus Evolve?
• What Is the Good News for HIV-Positive Patients?
• What Is the Impact of HIV on Society?
• What Are the Symptoms of HIV/Aids?
• How Long Will HIV Take to Show Up?
• Can Mosquitoes Transmit HIV?
• How Can You Get HIV?
• How Fast Does HIV Spread in the Body?
• What Can the Government Do to Stop HIV?
• When Did HIV First Arise?
• Why Are Child Victims of Sexual Abuse at Greater Risk of HIV?
• How Long Do HIV Symptoms Last?
• Will There Be a Cure for HIV by 2030?
• Can You Survive HIV-Positive?
• How Many Teenagers Are Affected by HIV?
• Is There Currently a Cure for HIV?
• What Age Group Has the Highest HIV Infection Rate?
• How Long Can You Live After Having HIV?
• What Are the Three Biggest Risk Factors for HIV?
• Which Antibody Functions Are Important for an HIV Vaccine?
• Can You Drink When HIV Positive?
• Why Is HIV Research Important?
• What Resources Are Available for HIV Patients?
• Chicago (A-D)
• Chicago (N-B)

IvyPanda. (2024, February 29). 264 HIV Essay Topic Ideas & Examples. https://ivypanda.com/essays/topic/hiv-essay-topics/

"264 HIV Essay Topic Ideas & Examples." IvyPanda , 29 Feb. 2024, ivypanda.com/essays/topic/hiv-essay-topics/.

IvyPanda . (2024) '264 HIV Essay Topic Ideas & Examples'. 29 February.

IvyPanda . 2024. "264 HIV Essay Topic Ideas & Examples." February 29, 2024. https://ivypanda.com/essays/topic/hiv-essay-topics/.

1. IvyPanda . "264 HIV Essay Topic Ideas & Examples." February 29, 2024. https://ivypanda.com/essays/topic/hiv-essay-topics/.

Bibliography

IvyPanda . "264 HIV Essay Topic Ideas & Examples." February 29, 2024. https://ivypanda.com/essays/topic/hiv-essay-topics/.

• AIDS Titles
• Cancer Essay Ideas
• Disease Questions
• Tuberculosis Questions
• Black Death Ideas
• Health Promotion Research Topics
• Communicable Disease Research Topics
• Infection Essay Ideas
• Human Papillomavirus Paper Topics
• Pandemic Ideas
• STDs Essay Topics
• Pathogenesis Research Ideas
• Viruses Research Topics
• Hepatitis Questions

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

Preview improvements coming to the PMC website in October 2024. Learn More or Try it out now .

• Advanced Search
• Journal List
• BMC Med Res Methodol

Abstracts reporting of HIV/AIDS randomized controlled trials in general medicine and infectious diseases journals: completeness to date and improvement in the quality since CONSORT extension for abstracts

Jean joel r. bigna.

1 Department of Epidemiology and Public Health, Centre Pasteur of Cameroon, Member of the International Network of the Pasteur Institute, Yaoundé, Cameroon

Jean Jacques N. Noubiap

2 Department of Medicine, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa

3 Medical Diagnostic Center, Yaoundé, Cameroon

Serra Lem Asangbeh

Lewis n. um.

4 Faculty of Medicine and Biomedical Sciences, University of Yaoundé 1, Yaoundé, Cameroon

Paule Sandra D. Sime

Elvis temfack.

5 Internal Medicine Unit, Douala General Hospital, Douala, Cameroon

6 Molecular Mycology Unit, Institut Pasteur of Paris, Paris, France

Mathurin Cyrille Tejiokem

Associated data.

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

Sufficiently detailed abstracts of randomized controlled trials (RCTs) are important, because readers often base their assessment of a trial solely on information in the abstract. We aimed at comparing reporting quality of RCTs in HIV/AIDS medicine before and after the publication of the 2008 CONSORT extension for abstracts and to investigate factors associated with better reporting quality.

We searched PubMed/Medline for HIV/AIDS RCTs published between 2006–07 (Pre-CONSORT) and 2014–15 (Post-CONSORT) in 40 leading general medicine and infectious diseases journals. Two investigators extracted data and scored abstracts. The primary outcome was the adjusted mean number of items reported among the 17 required. Proportions of abstracts reporting each of 17 items were considered as secondary outcome. The adjustment was done for journal field, CONSORT endorsement, abstract format, type of intervention, journal impact factor and authorship. This study received no funding.

The adjusted mean number of reported items was 7.2 (95 % CI 6.6–7.7) in pre-CONSORT ( n  = 159) and 7.8 (95 % confidence interval [CI] 7.3–8.4) in post-CONSORT ( n  = 153) (mean difference 0.7; 95 % CI 0.1–1.2). Journal high impact factor (adjusted incidence rate ratio 2.16; 95 % CI 1.83–2.54), abstract with 13 authors or more (1.39; 95 % CI 1.07–1.79) and non-pharmacological intervention (1.19; 95 % CI 1.03–1.37) were independent factors for better reporting quality. There were significant improvements in reporting on participants, randomization, outcome results, registration and funding; regression for author contact; and no change for other items: title, design, interventions, objective, primary outcome, blinding, number randomized, recruitment, number analyzed, harms and conclusions.

Conclusions

After the publication of the CONSORT extension for abstracts, the reporting quality of HIV/AIDS RCT abstracts in general medicine and infectious diseases journals has suboptimally improved. Thus, stricter adherence to the CONSORT for abstract are needed to improve the reporting quality of HIV/AIDS RCT abstracts.

Electronic supplementary material

The online version of this article (doi:10.1186/s12874-016-0243-y) contains supplementary material, which is available to authorized users.

Randomized controlled trials (RCTs) which are designed to provide the best quality of evidence required for health care decisions [ 1 , 2 ] should ideally be reported according to pre-defined standards. Most readers of articles reporting RCT usually start by making an initial assessment of the interest of the article after reading the content of the abstract, which subsequently guides the decision on whether to read the entire article or not [ 3 ]. With an overwhelming day-to-day workload, the continuous availability of large volumes of new scientific publications, limited access to many full-text articles (particularly in resource limited settings) [ 4 ], many health professionals tend to make recourse to information on abstracts to take health care decisions [ 3 ]. As such abstracts of trials reported in journals should contain sufficiently accurate and clear information that permits the reader to get a good synopsis of the findings of the trial [ 5 ]. Formerly, there was no standardized method of reporting RCT and this created many discordances in the reporting of RCTs. These discrepancies, stimulated the establishment of the Consolidated Standards of Reporting Trials (CONSORT) statement, the first of which was published in 1996 and revised in 2001 [ 6 , 7 ], which aimed at “standardizing” and improving the way RCTs are reported [ 8 ]. In order to avoid inconsistencies between the content of the abstract and the full text of the article, as was seen in many RCT reports, an extension to the CONSORT statement was published in 2008, which provided a list of essential items to be included for reporting of abstracts of RCTs [ 9 ]. This statement comprises seventeen items distributed in eight sections which include: the title, authors contact details, trial design, methods (participants, interventions, objective, outcomes, randomization, blinding), results (numbers randomized, recruitment, numbers analyzed, outcome, harms), conclusions, trial registration and funding [ 9 ].

Following the publication of this CONSORT extension for abstract reporting, studies to assess the quality of abstract reporting in general medicine journals and other specific fields of medicine have been done. These studies have shown that there is substantial room for improvement in the adherence to these reporting guidelines [ 10 – 19 ].

However, as concerns RCTs in HIV/AIDS medicine, there are limited studies investigating the impact of CONSORT extension for abstract reporting checklist. In this field of HIV/AIDS where guidelines to tackle the pandemic are continually changing, adherence to this statement is particularly important, most especially as HIV/AIDS disproportionally affects resource limited settings (mainly sub-Saharan African countries) where most of the RCTs are done but most of health professionals do not have access to full-text articles required for health care decision making. We therefore, in the present study, using abstracts of the periods before and after the publication of CONSORT extension for abstracts, aim to first of all compare the overall reporting quality of RCTs in HIV/AIDS medicine published in general medicine and infectious diseases journals, and secondly determine the factors associated with better reporting quality.

We conducted a systematic review of abstracts published in 2006, 2007, 2014 and 2015 in 20 leading general medicine and 20 leading infectious diseases journals based on 2014 impact factor.

Data sources

We conducted a MEDLINE/PubMed search of all RCTs published in the years 2006–2007 and 2014–2015. The search strategy used MeSH terms like “randomized controlled trial” as publication type, journal names and HIV and AIDS as terms in title/abstract. We limited search for the following periods: (2006/01/01 to 2007/12/31 and 2014/01/01 to 2015/12/31). The choice of the time limit of 2014 and 2015 was arbitrary and based on the fact that 6 years after the publication of the first CONSORT statement for abstracts in 2008, is sufficient time for researchers to have become versed with the recommendations. Other types of articles (editorial, case reports, comment, observational study, review, meta-analysis and letters) were excluded. Searches were done regularly during the study period and the last one was conducted on February 26, 2016 as could be seen presented in Additional file 1 .

Studies selection

RCT abstracts where interventions were provided to HIV-infected patients were selected. These abstracts were included when participant allocation to interventions was described by the terms “random”, “randomly allocated”, “randomized”, “randomization” or another word in the abstract suggesting that participants were randomly distributed between the trial arms. We considered journals as CONSORT statement endorser if they referenced CONSORT statement in their ‘Instruction to authors/Submission guidelines’ or if they reference as endorser in the CONSORT webpage ( http://www.consort-statement.org/about-consort/consort-endorsement/consort-endorsers---journals/ ). Two reviewers independently selected abstracts.

Data extraction and covariates

Data extraction was independently done by two reviewers using a pre-made and pretested data extraction form in compliance with the items of the recommendations of the evaluation of RCTs using the CONSORT for abstracts [ 9 ]. Each question had a ‘yes’ or ‘no’ response for each item indicating whether the authors had reported it or not. Agreement between the two reviewers was measured using the Kappa statistic [ 20 ] and discrepancies were resolved by discussion among the authors or by arbitration of a third author. Other information collected from journals other than the CONSORT abstracts items, were journal name, type of abstract format (IMRAD [introduction, method, results and discussion] or eight-heading [objective, design, setting, participants, intervention, main outcome measure, results and conclusions] or one-block), type of interventions in the trial (pharmacological or non-pharmacological), number of authors, publication on behalf of a research collaboration group, and journal field (infectious diseases or general medicine).

Main outcomes definition

The primary outcome was the number of items reported in each selected abstract. The secondary one was the proportion of abstracts reporting each of 17 recommended items.

Statistical analysis

IBM Statistical Package for Social Science (IBM SPSS) version 23.0 for Windows (IBM Corp. Released 2014. IBM SPSS Statistics for Windows, Version 23.0. Armonk, NY: IBM Corp.) was used to code, enter and analyze data. Categorical variables were expressed as numbers with percentages (%). Continuous variables were expressed as means with standard deviation.

We expressed the number of items for each year as mean (standard deviation [SD]). We estimated mean differences using the independent two-sample T -test for unadjusted means and the generalized estimation equations (GEEs) for adjusted means [ 21 ]. All these mean differences were reported with 95 % confidence intervals (95 % CI). The χ 2 was used to compare compliance with the 17 items of CONSORT extension for abstracts between pre-CONSORT and post-CONSORT for abstracts publication. This was also done using GEE for adjusted analysis. We reported measures of association as odd ratios (OR) for univariate analyses and as adjusted odds ratios (aOR) for multivariate analyses both with their 95 % CI. A p-value < 0.05 was considered statistically significant.

Incidence rate ratios (IRRs) were computed to identify factors associated with better reporting in 2014–15 abstracts using GEE. For this analysis, Poisson distribution and unstructured correlation matrix were assumed. Univariate and multivariate analyses were conducted.

For GEE, adjustments were made for CONSORT endorser journal (yes/no), abstract format (IMRAD/8-heading/one-block), publication on behalf of a group (yes/no), number of authors (≤6/7–12/≥ 13), and journal field (general medicine/infectious diseases). Journal name has been used as grouping factor due to fact that they can similarity in articles published in the same journal. The adjustment was done for abstract format because there are previous studies reporting relationship between abstract format and quality reporting [ 15 , 22 ]. The adjustment was also done for number of authors and publication on behalf a group because it was reported an association with higher quality of work with number of collaborators [ 23 , 24 ].

General characteristics of selected abstracts

Our search yielded 444 articles of which 95 were published in 2006, 103 in 2007, 140 in 2014 and 106 in 2015. One hundred and thirty-two abstracts did not meet our inclusion criteria, hence were excluded. We therefore included 76 abstracts from 2006, 83 from 2007 (2006–07, n  = 159), 81 from 2014 and 72 from 2015 ( n  = 153) as shown in the flow diagram (Fig.  1 ).

Flow chart of included studies

The inter-observer agreement value was 0.86 for abstract selection, 0.71 for overall rating of abstract reporting quality, and varied between 0.74 and 0.98 for each items of CONSORT for abstracts.

All articles came from 19 of 40 journals included in search strategy. Interventions were pharmacological/vaccine in 76 % (238/312) of the abstracts. The IMRAD format was used in 85 % (266/312) of abstracts. Among all the journals, 84 % of abstracts (262/312) were from journals which endorsed CONSORT, 80 % (248/312) were from infectious diseases journals, 63.5 % (198/312) were published on behalf of a group, and 75 % (233/312) were published in journals with impact factor less than 10. The mean number of authors among articles was 12.2 (SD 6.8) (Table  1 ).

Distribution of HIV abstracts by year and characteristics

There were no abstract for the following journals included in search strategy: AIDS Review, The American Journal of Medicine, American Journal of Preventive Medicine, Annals of Family Medicine, Annals of Medicine, Canadian Medical Association Journal, Clinical Microbiology and Infection, Cochrane Database of Systematic Reviews, Current Opinion in HIV and AIDS, Current Opinion in Infectious Diseases, Emerging Infectious Diseases journal, Eurosurveillance, Infection and Immunity, Infection Control and Hospital Epidemiology, Journal of Cachexia Sarcopenia Muscle, Journal of infection, Journal of Internal Medicine, Mayo Clinic Proceedings, Medicine and Translational Research

Overall quality of reporting

Only 1 % (2/153) of abstracts reported all items in the 2014–15 period. The mean number of items reported in 2006–07 (6.2; SD = 2.5; Median 6; Range 1–14) differed significantly from that reported in 2014–15 (7.7; SD = 4.0; Median 7; Range 1–17), mean difference (MD): 1.6; 95 % CI 0.8–2.3; p <0.001.

In the GEE analysis, after adjusting for covariates among the type of intervention, journal endorser of CONSORT, format of abstract, journal field, numbers of authors, journal impact factor and publication on a behalf of a group, the adjusted mean number of items reported in 2006–07 (7.2; 95 % CI 6.6–7.7) differed significantly from that reported in 2014–15 (7.8; 95 % CI 7.3–8.4), adjusted MD: 0.7; 95 % CI 0.1–1.2; p = 0.015.

Quality of reporting of each item

In univariate analysis, there was improvement from 2006–07 to 2014–15 for ‘title’, ‘trial design’, ‘participants’, ‘objective’, ‘randomization’, ‘blinding’, ‘recruitment’, ‘number analyzed’, ‘outcome’, ‘conclusion’, ‘trial registration’ and ‘funding’. However, the quality of abstracts decreased for ‘author contact’. After adjustment, the quality of abstract remained improved for the following items: ‘participants’ (aOR 1.92; 95 % CI 1.05–3.51), ‘randomization’ (p < 0.001), ‘outcome’ of results section (aOR 2.26; 95 % CI 1.17–4.35), ‘trial registration’ (aOR 8.32; 95 % CI 3.66–10.88) and ‘funding’ (p < 0.001). From the 2006–07 period to the 2014–15 period, the quality of the item ‘author contact’ decreased (aOR 0.06; 95 % CI 0.03–0.12) (Table  2 ).

Crude and adjusted odds ratios for adherence to the 12 items of the CONSORT statement for HIV/AIDS abstracts in 2014–2015 compared to 2006–2007

CI confidence interval

a Chi squared tests

b Generalized estimation equations with journal as grouping variable: adjustment has been made for journal impact factor (<10 versus ≥ 10), journal field (general medicine versus infectious diseases), CONSORT endorser journal (yes versus no), abstract format (IMRAD/eight-heading/one-block), type of intervention (pharmacological versus non pharmacological), number of authors (less than 6/7–12/more than 13); expect for title and author contact in which abstract format was not considered

Factors associated with better reporting quality in 2014–2015 abstracts

In univariate analysis, factors associated with better reporting included publishing in general medicine journal, publishing in CONSORT endorser journals, structured abstract (IMRAD or 8-heading), high impact journal, more than 13 authors and publishing on behalf of a research collaboration group. In multivariate analysis, factors independently associated with better reporting of abstracts in 2014–15 included publishing on non-pharmacological/vaccine intervention (aIRR 1.19; 95 % CI 1.03–1.37), more than 13 authors (aIRR 1.39; 95 % CI 1.07–1.79) and high journal impact factor (aIRR 2.16; 95 % CI 1.83–2.54) (Table  3 ).

Unadjusted and adjusted incidence rate ratios for the total number of CONSORT extension for HIV abstract items reported

CI confidence interval, CONSORT consolidated standards of reporting trials, IMRAD introduction, methods, results and discussion

This study aimed to assess, according to the CONSORT for abstract checklist, the differences in the reporting quality of abstracts of RCTs in HIV/AIDS medicine published in general medicine and infectious diseases journals before (in the years 2006–07) and after (in the years 2014–15) the publication of the CONSORT extension for abstracts [ 9 ]. Our findings demonstrate that for some items (participants, randomization, outcome of results section, trial registration and funding), the reporting quality of HIV/AIDS RCT abstracts has improved significantly in the post-CONSORT era as compared to the pre-CONSORT era, while for others the quality has remained unchanged or regressed (authors contact). These results are consistent with previous studies that have reported inconsistencies and patterns of non-compliance to the CONSORT for abstracts guidelines in most of journals [ 10 – 19 ].

The mean number of items reported increased significantly from 2006–07 to 2014–15. This is in line with the average of 3 more items reported in RCT abstracts in top-tiers of general medicine journals since 2008 as found in a recent study [ 19 ]. High impact factor was independently associated with more adherence to CONSORT abstract items as in a study in which high impact factor is associated with high quality reporting for CONSORT items [ 15 , 25 – 30 ]. Many people and institutions consider journal impact factor as the reflect of articles’ quality [ 31 ]. High number of authors was also independently associated with more adherence to CONSORT abstract items as in previous studies [ 23 , 24 ]. One can argue that the involvement of a large number of authors in an article could improve quality. Many authors would increase the chances that one or more of the authors ensure to the respect of the reporting guidelines. We also found non pharmacological/vaccine intervention in trial a factor for better reporting. This finding requires more investigation to understand this relationship.

As a whole, the reporting of some items improved significantly over time: more abstracts in 2014–15 as compared to 2006–07 identified the study as randomized in the title, provided details on the trial design, randomization, blinding, trial registration and funding. For most abstract elements there was progress in reporting even though this was not significant. One of the main reasons that can explain the improvement of the overall reporting quality of abstracts found in our study is the endorsement of the CONSORT statement by most of the journals surveyed. Indeed, 84 % of articles included in our analysis were published in journals that endorsed CONSORT. A systematic review that examined the effectiveness of the CONSORT statement in journals that have formally endorsed it concluded that journals’ adoption of CONSORT is associated with improved reporting of RCTs [ 8 ]. Moreover, another study has also shown that the endorsement of recommendation and effective implementation of CONSORT guidelines lead to the improvement of reporting quality of abstracts [ 12 ]. In line with these studies, our findings stress the need to expand journal endorsement and implementation of the CONSORT extension for abstracts before manuscript submission (in journal submission guidelines), during review process and editorial assessment. Authors should be required to submit a completed CONSORT checklist with each manuscript with an emphasis for CONSORT extension for abstracts [ 32 ]; reviewers should assess the completeness of abstract reporting; and final manuscript copyediting would surely improve abstract reporting quality [ 19 ].

Despite this overall improvement, the quality of reporting of some items remained sub-optimal, consistent with findings from other studies [ 10 – 19 ]. Poorly reported items specifically include methods of randomization and allocation concealment, and blinding. These items are essential methodological elements which are critical, therefore adequate standardized reporting is indispensable so as to demonstrate that selection bias was avoided, thereby allowing unequivocal interpretations of the study findings [ 5 ]. Nevertheless, less abstracts in 2014–15 reported corresponding authors’ details (postal and email addresses). This is a major drawback when readers need to contact authors for further information on the study. This depends on journal indexing policy, rather than a deficiency in reporting. In addition, author contact details are more relevant for conference abstracts, none of which were included in this study [ 5 ].

Though we found that there has been some improvement in HIV RCT abstract reporting, our study had some limitations. We not investigated others factors that can influence reporting quality. These non-investigated factors include abstract word count, types of utilization of CONSORT guidelines in the ‘instructions for authors’ section of journals, and awareness of the CONSORT statement. Furthermore, this study reports on the adequacy of reporting using the CONSORT checklist items, but the accuracy of reporting cannot be assured because a comparison of the abstract and the full text was beyond our scope.

The reporting quality of RCT abstracts in HIV/AIDS medicine in general medicine and infectious diseases journals has sub-optimally improved after the publication of the CONSORT extension for abstracts. This suboptimal improvement is associated with journal high impact factor, high number of authors and non-pharmacological/vaccine intervention in the trial. However, there is still much to do for improvement to meet the standards of the CONSORT for abstracts guidelines. Journal endorsement and more strict adherence to the CONSORT for abstracts standards by both authors and journal editors will contribute to better RCT reports in HIV/AIDS medicine. Further researches are necessary to investigate why authors, reviewers, journal editors, funders, institutions and readers not fully adhere to CONSORT guidelines.

Acknowledgements

None to declare.

This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

Availability of data and materials

Authors’ contributions.

Study conception and design: JJRB and JJNN. Data collection: JJRB. Abstract selection: LNU, PSDS and JJRB. Data extraction: LNU, PSDS and JJRB. Statistical analysis: JJRB. Data interpretation: JJRB, JJNN, SLA, ET and MCT. Drafting: JJRB and JJNN. Critical discussion and manuscript revision: All authors. Approved the final version of the manuscript: All authors.

Competing interests

The authors declare that they have no competing interests.

Consent for publication

Not applicable.

Ethics approval and consent to participate

Abbreviations, additional file.

Search strategy for HIV RCTs published in 2006–2007 and 2014–2015 in leading general medicine and infectious diseases journals. (DOCX 14 kb)

Contributor Information

Jean Joel R. Bigna, Email: rf.oohay@jjmirangib .

Jean Jacques N. Noubiap, Email: rf.oohay@jjpaibuon .

Serra Lem Asangbeh, Email: moc.liamg@88melarres .

Lewis N. Um, Email: rf.oohay@eboynmul .

Paule Sandra D. Sime, Email: rf.oohay@emisardnas .

Elvis Temfack, Email: moc.liamtoh@kcafmete .

Mathurin Cyrille Tejiokem, Email: rf.oohay@ycamet .