Estimating HIV pre-exposure prophylaxis need and impact in Malawi, Mozambique and Zambia: A geospatial and risk-based analysis.

BACKGROUND: Pre-exposure prophylaxis (PrEP), a WHO-recommended HIV prevention method for people at high risk for acquiring HIV, is being increasingly implemented in many countries. Setting programmatic targets, particularly in generalised epidemics, could incorporate estimates of the size of the population likely to be eligible for PrEP using incidence-based thresholds. We estimated the proportion of men and women who would be eligible for PrEP and the number of HIV infections that could be averted in Malawi, Mozambique, and Zambia using prioritisation based on age, sex, geography, and markers of risk. METHODS AND FINDINGS: We analysed the latest nationally representative Demographic and Health Surveys (DHS) of Malawi, Mozambique, and Zambia to determine the proportion of adults who report behavioural markers of risk for HIV infection. We used prevalence ratios (PRs) to quantify the association of these factors with HIV status. Using a multiplier method, we combined these proportions with the number of new HIV infections by district, derived from district-level modelled HIV estimates. Based on these numbers, different scenarios were analysed for the minimum number of person-years on PrEP needed to prevent 1 HIV infection (NNP). An estimated total of 38,000, 108,000, and 46,000 new infections occurred in Malawi, Mozambique, and Zambia in 2016, corresponding with incidence rates of 0.43, 0.63, and 0.57 per 100 person-years. In these countries, 9%-20% of new infections occurred among people with a sexually transmitted infection (STI) in the past 12 months and 40%-42% among people with either an STI or a non-regular sexual partner (NP) in the past 12 months (STINP). The models estimate that around 50% of new infections occurred in districts with incidence rates ≥1.0% in Mozambique and Zambia and ≥0.5% in Malawi. In Malawi, Mozambique, and Zambia, 35.1%, 21.9%, and 12.5% of the population live in these high-incidence districts. In the most parsimonious scenario, if women aged 15-34 years and men 20-34 years with an STI in the past 12 months living in high-incidence districts were to take PrEP, it would take a minimum of 65.8 person-years on PrEP to avert 1 HIV infection per year in Malawi, 35.2 in Mozambique, and 16.4 in Zambia. Our findings suggest that 3,300, 5,200, and 1,700 new infections could be averted per year in the 3 countries, respectively. Limitations of our study are that these values are based on modelled estimates of HIV incidence and self-reported behavioural risk factors from national surveys. CONCLUSIONS: A large proportion of new HIV infections in these 3 African countries were estimated to occur among people who had either an STI or an NP in the past year, providing a straightforward means to set PrEP targets. Greater prioritisation of PrEP by district, sex, age, and behavioural risk factors resulted in lower NNPs thereby increasing PrEP cost-effectiveness, but also diminished the overall impact on reducing new infections.

Earlier treatment initiation is associated with a decreased number of HIV-1 subtype A1 transmissions in Greece.

OBJECTIVES: Subtypes A1 and B are the most prevalent HIV-1 clades in Greece. Subtype A1 epidemic is highly monophyletic and corresponds to transmissions that occurred locally. Our aim in this molecular epidemiology analysis was to investigate the role of early treatment in preventing new HIV-1 transmissions. METHODS: Our analysis focused on 791 subtype A1 sequences from treatment-naïve individuals in Greece. Estimation of infection dates was performed by molecular clock calculations using Bayesian methods. We estimated the time interval between (1) the infection and sampling dates (linkage to care window), (2) the sampling dates and antiretroviral therapy (ART) initiation (treatment window), and (3) the infection dates and ART initiation (transmissibility window) for the study population. We also inferred the putative source of HIV infections between individuals of different groups divided according to the length of treatment, linkage to care or transmissibility window. RESULTS: A significant decline was detected for the treatment window during 2014-2015 versus the 2 previous years (p=0.0273), while the linkage to care interval remained unchanged during the study period. Inference of the putative source of HIV infections suggested that individuals with a recent diagnosis or narrow transmissibility window (time period between HIV infection and ART initiation) were not sources of HIV infections to other groups. Contrarily, a significant number of HIV infections originated from individuals with longer transmissibility window interval. CONCLUSIONS: Our findings showed that the treatment window is decreasing over time, presumably due to the updated treatment guidelines. Our study also demonstrates that people treated earlier after infection do not transmit at high rates, thus documenting the benefits of early ART initiation in preventing ongoing HIV-1 transmission.

HIV prevention and treatment in Southern Europe in the aftermath of bailout programmes.

BACKGROUND: The global financial crisis impacted public health in Europe, and had a particularly critical detriment to health systems in Southern Europe. We aim to describe HIV response and progress towards the current global HIV targets in specific Southern European countries, which received financial adjustment programmes. METHODS: We examined and compared a set of HIV indicators in Cyprus, Greece, Portugal and Spain. The indicators included: (i) HIV epidemiology; (ii) adoption of WHO's 'Treat All' recommendation; (iii) progress towards the UNAIDS global targets of 90-90-90; (iv) adoption/implementation of pre-exposure prophylaxis (PrEP); and (v) adoption/implementation of WHO's HIV self-testing (HIVST) recommendation. RESULTS: HIV incidence varied across countries since 2010, with sustained declines in Portugal and Spain, and marked increases in Greece and Cyprus. By 2016, all four countries have adopted WHO's 'Treat All' recommendation, leading to a marked increase in people receiving ART. Improvements were seen in all 90-90-90 targets, with Portugal achieving those in 2017, but Greece lagging somewhat behind, as of 2016. Portugal and Spain have also started implementing PrEP, and Greece has completed a pilot with no additional access to PrEP for pilot participants and no national programme in place. Cyprus has been the slowest in terms of adopting PrEP and HIVST. CONCLUSIONS: Countries need to focus on prioritizing effective and comprehensive prevention measures, including HIVST and PrEP, and scale-up access to quality treatment and care for those diagnosed, in order to accelerate the reduction of new HIVs infections and successfully meet the global targets for HIV treatment.

HIV incidence among men who have sex with men at a community-based facility in Greece.

OBJECTIVE: Men who have sex with men (MSM) are disproportionately affected by HIV in Greece. However, research on HIV incidence in this group is lacking. This study aimed at estimating HIV incidence among MSM in Athens, Greece. METHODS: The analysis included routinely collected data between January 2013-June 2015 from adult MSM who visited a community-based facility (Ath Checkpoint) at least twice and were non-reactive to the rapid INSTITM HIV-1/HIV-2 assay at baseline. HIV conversion rates were calculated by dividing the number of clients who became reactive by the person-years of observation. All statistical analyses including Poisson regression models were conducted in STATA 14. RESULTS: A total of 1,243 MSM contributed 1,102.50 person-years (py). The overall (per 100 py) conversion rate was 3.99 (95% CI: 2.97-5.36). In multivariable analyses, age less than 30 years was associated with an increased risk of HIV conversion (rate ratio: 2.01; 95% CI: 1.08-3.76). CONCLUSIONS: This analysis shows high rates of HIV conversion among MSM who repeatedly visit a community-based testing site. Ath Checkpoint could contribute to HIV surveillance and identify a high-risk group that could benefit from essential health interventions.

Molecular Tracing of the Geographical Origin of Human Immunodeficiency Virus Type 1 Infection and Patterns of Epidemic Spread Among Migrants Who Inject Drugs in Athens.

BACKGROUND: High numbers of human immunodeficiency virus type 1 (HIV-1) infections among people who inject drugs (PWID) have been diagnosed in Athens, Greece, since 2011. We aimed to trace the geographic origin of HIV-1 infection for migrants who inject drugs and to investigate whether transmissions occur more frequently among migrants than among Greek nationals. METHODS: Multiple cross-sectional studies were pooled to assemble all persons diagnosed with HIV-1 in Greece between 1 January 2011 and 31 October 2014. Phylogenetic analyses used maximum likelihood estimation. The hypothesis of ethnic compartmentalization was tested by reconstructing ancestral states of characters at the tips using the criterion of parsimony over a set of bootstrap trees. RESULTS: Of 2274 persons, 38.4% were PWID. Phylogenetic analyses showed the existence of 4 major PWID-specific local transmission networks (LTNs): CRF14_BG (437 [58.6%]), CRF35_AD (139 [18.6%]), subtype B (116 [15.6%]), and subtype A (54 [7.2%]). Of 184 non-Greek PWID, 78.3% had been infected within the PWID-LTNs. For 173 (94.3%), the origin of their infection was assumed to be in Greece (postmigration). For PWID infected within LTNs, transmissions for subtype A and CRF14_BG occurred more frequently among migrants than would be expected by chance (phyloethnic study). CONCLUSIONS: Our analysis showed that the majority of infections among migrants occurred postmigration. The existence of significant transmission networking among migrants highlights that this population is a priority for HIV prevention. As molecular analysis can estimate the probable country of HIV infection, it can help to inform the design of public health strategies.

Values and Preferences on the Use of Oral Pre-exposure Prophylaxis (PrEP) for HIV Prevention Among Multiple Populations: A Systematic Review of the Literature.

Daily oral pre-exposure prophylaxis (PrEP) is the use of antiretroviral drugs by HIV-negative people to prevent HIV infection. WHO released new guidelines in 2015 recommending PrEP for all populations at substantial risk of HIV infection. To prepare these guidelines, we conducted a systematic review of values and preferences among populations that might benefit from PrEP, women, heterosexual men, young women and adolescent girls, female sex workers, serodiscordant couples, transgender people and people who inject drugs, and among healthcare providers who may prescribe PrEP. A comprehensive search strategy reviewed three electronic databases of articles and HIV-related conference abstracts (January 1990-April 2015). Data abstraction used standardised forms to categorise by population groups and relevant themes. Of 3068 citations screened, 76 peer-reviewed articles and 28 conference abstracts were included. Geographic coverage was global. Most studies (N = 78) evaluated hypothetical use of PrEP, while 26 studies included individuals who actually took PrEP or placebo. Awareness of PrEP was low, but once participants were presented with information about PrEP, the majority said they would consider using it. Concerns about safety, side effects, cost and effectiveness were the most frequently cited barriers to use. There was little indication of risk compensation. Healthcare providers would consider prescribing PrEP, but need more information before doing so. Findings from a rapidly expanding evidence base suggest that the majority of populations most likely to benefit from PrEP feel positively towards it. These same populations would benefit from overcoming current implementation challenges with the shortest possible delay.

Phylogeographical footprint of colonial history in the global dispersal of human immunodeficiency virus type 2 group A.

Human immunodeficiency virus type 2 (HIV-2) emerged in West Africa and has spread further to countries that share socio-historical ties with this region. However, viral origins and dispersal patterns at a global scale remain poorly understood. Here, we adopt a Bayesian phylogeographic approach to investigate the spatial dynamics of HIV-2 group A (HIV-2A) using a collection of 320 partial pol and 248 partial env sequences sampled throughout 19 countries worldwide. We extend phylogenetic diffusion models that simultaneously draw information from multiple loci to estimate location states throughout distinct phylogenies and explicitly attempt to incorporate human migratory fluxes. Our study highlights that Guinea-Bissau, together with Côte d'Ivoire and Senegal, have acted as the main viral sources in the early stages of the epidemic. We show that convenience sampling can obfuscate the estimation of the spatial root of HIV-2A. We explicitly attempt to circumvent this by incorporating rate priors that reflect the ratio of human flow from and to West Africa. We recover four main routes of HIV-2A dispersal that are laid out along colonial ties: Guinea-Bissau and Cape Verde to Portugal, Côte d'Ivoire and Senegal to France. Within Europe, we find strong support for epidemiological linkage from Portugal to Luxembourg and to the UK. We demonstrate that probabilistic models can uncover global patterns of HIV-2A dispersal providing sampling bias is taken into account and we provide a scenario for the international spread of this virus.

Self-Testing as an Invaluable Tool in Fighting the COVID-19 Pandemic.

OBJECTIVES: The United Kingdom and a number of European Union countries are offering and distributing rapid antigen detection tests (RADTs) for self-test use to detect SARS-CoV-2. For instance, Greece, in the midst of its third wave of COVID-19, announced the provision of RADTs for self-testing through retail pharmacies. With the aim to determine the acceptability and feasibility of COVID-19 self-testing, we ran a cross-sectional survey on residents of Greece and Cyprus, aged over 18 years. METHODS: An online survey using the JISC platform was distributed to 1000 individuals who completed the survey anonymously. Data was collated and analyzed for complete responses by chi-squared and logistic regression analyses. RESULTS: A total of 248 complete responses were obtained, with balanced gender distribution and particular demographics representative of the 2 countries. The majority of participants (79%; n = 196) reported willingness to self-test and the remaining individuals reported no (10.5%; n = 26) or don't know (10.5%; n = 26). Being a university graduate significantly predicted the likelihood of being willing to self-test (odds ratio [OR] = 3.455, P < .001). Pearson Chi-square test found significant differences between university graduates versus non-graduates on the type of COVID-19 test preferred (χ2 = 8.95, df = 3, P < .03); graduates were more likely to prefer saliva testing and less likely to prefer the finger prick test than non-graduates. CONCLUSIONS: Our survey data evidences the acceptability of home-based self-testing, with a preference for saliva as choice of biological material for sampling. A number of factors, such as accessible reporting, contact tracing infrastructures, central registration, and validation for the implementation of different RADTs need to be taken collectively into consideration before self-testing can be universally and reliably scaled up.

Appraisal of a Contact Tracing Training Program for COVID-19 in Greece Focusing on Vulnerable Populations.

BACKGROUND: Contact tracing as an epidemiological strategy has repeatedly contributed to the containment of various past epidemics and succeeded in controlling the spread of disease in the community. Systematic training of contact tracers is crucial in ensuring the effectiveness of epidemic containment. METHODS: An intensive training course was offered to 216 health and other professionals who work with vulnerable population groups, such as Roma, refugees, and migrants in Greece, by the scientific team of the postgraduate programme "Global Health-Disaster Medicine" of the Medical School, National and Kapodistrian University of Athens, with the support of the Swiss embassy in Greece. The course was delivered online due to the pandemic restriction measures and was comprised of 16 h over 2 days. The course curriculum was adapted in Greek using, upon agreement, a similar training course to what was developed by the Johns Hopkins University Bloomberg School of Public Health. Evaluation of the course was conducted in order to determine the short term satisfaction from participating in this training course. RESULTS: A total of 70% of the course participants completed the evaluation questionnaires and all trainers gave feedback on the course. The training modules were ranked as extremely useful by the majority of the participants and over 50% of the participants specifically stated that the course content was directly related to their work with vulnerable groups. Content about the ethics of contact tracing and the effective communication skills presented were deemed most useful. CONCLUSION: The course was well organised and provided the required skills for effective contact tracing. Many course participants intend to use some components in their work with vulnerable populations groups. Contact tracing efforts work best in a systematic and coordinated way and the provision of systematic and organised training can greatly increase its effectiveness.

Lamivudine/Tenofovir Disoproxil Fumarate is an Appropriate PrEP Regimen.

Oral pre-exposure prophylaxis (PrEP) containing tenofovir disoproxil fumarate (TDF) co-formulated with emtricitabine (FTC) or lamivudine (3TC) is recommended as an additional prevention option for persons at substantial risk of HIV infection by both the World Health Organization (WHO) and the US President's Emergency Plan for AIDS Relief (PEPFAR). The WHO and PEPFAR consider 3TC clinically interchangeable with FTC for PrEP given comparable pharmacologic equivalence, resistance and toxicity patterns, and indirect clinical trial evidence from TDF-containing studies. Globally, FTC/TDF has been widely used in clinical trials, open-label extension studies and demonstration projects. Thus, most PrEP efficacy and safety data are based on FTC/TDF use in heterosexual women and men, men who have sex with men, and people who inject drugs. However, generic 3TC/TDF is less expensive than FTC/TDF, is already available in supply chains for HIV drugs, and has 60-70% of the global adult market share, making it particularly appealing in settings with limited availability or affordability of FTC/TDF. Compelling indirect evidence suggests that scaling up use of 3TC/TDF is potentially cost saving for HIV programs in settings where restricting drug choice to FTC/TDF would delay PrEP implementation. Guideline committees and public health decision-makers in countries should encourage flexibility in PrEP drug selection, support off-label use of 3TC/TDF, and approve use of generic formulations to decrease the cost of PrEP medications and accelerate PrEP delivery through the public and private sectors.

Pre-Exposure Prophylaxis for HIV Prevention in Women: Current Status and Future Directions.

Pre-exposure prophylaxis (PrEP) is a promising intervention to prevent HIV acquisition, with benefits both to the individual and to population-level health. PrEP is an opportunity to complement ongoing public health efforts to eliminate HIV. For women, PrEP can also serve as a gateway to access sexual and reproductive health (SRH) services. Clinical efficacy of PrEP was initially reported in women using a 1% tenofovir vaginal gel in 2010, followed by an efficacy trial of oral PrEP using TDF/FTC in men who have sex with men (MSM). Since then, further trials have reported efficacy in oral PrEP containing tenofovir in women and heterosexual men, while the subsequent trials for women using tenofovir gel reported no efficacy, stemming from difficulties in achieving adequate adherence. In an effort to offer women additional choices to oral PrEP, alternative modalities are being tested in clinical research, including long-acting injectable formulations and intra-vaginal rings. In 2015, a meta-analysis of clinic trials and open-label extension studies led to the World Health Organization (WHO) strongly recommending the provision of oral PrEP containing tenofovir for any person at substantial risk of HIV infection, irrespective of gender or population group. Currently, PrEP services for women around the world, including those who are either pregnant or breastfeeding, remain limited. Outside sub-Saharan Africa, most PrEP programmes are focused on MSM. South Africa, Kenya, and the USA have the greatest utilization of oral PrEP by women. Yet, since 2012, of the estimated > 300,000 people globally who have initiated PrEP, a minority are women. In this narrative review, we examine the most recent literature on clinical and implementation PrEP research among women. We highlight the high burden of disease related to common sexually transmitted infections (STIs) in women, and the opportunity to integrate PrEP and other HIV prevention services, STI case management, and family planning services, as part of a more robust package of SRH services. Raising awareness on PrEP amongst women and their healthcare providers, minimizing gaps in access, and ensuring adherence and persistence of PrEP during periods of risk are critical issues if PrEP can have a meaningful impact on reducing HIV incidence in women globally.

Global Epidemiologic Characteristics of Sexually Transmitted Infections Among Individuals Using Preexposure Prophylaxis for the Prevention of HIV Infection: A Systematic Review and Meta-analysis.

Importance: Despite a global increase in sexually transmitted infections (STIs), there is limited focus and investment in STI management within HIV programs, in which risks for STIs are likely to be elevated. Objective: To estimate the prevalence of STIs at initiation of HIV preexposure prophylaxis (PrEP; emtricitabine and tenofovir disoproxil fumarate) and the incidence of STIs during PrEP use. Data Sources: Nine databases were searched up to November 20, 2018, without language restrictions. The implementers of PrEP were also approached for additional unpublished data. Study Selection: Studies reporting STI prevalence and/or incidence among PrEP users were included. Data Extraction and Synthesis: Data were extracted independently by at least 2 reviewers. The methodological quality of studies was assessed using the Joanna Briggs Institute critical assessment tool for prevalence and incidence studies. Random-effects meta-analysis was performed. Main Outcomes and Measures: Pooled STI prevalence (ie, within 3 months of PrEP initiation) and STI incidence (ie, during PrEP use, after 3 months). Results: Of the 3325 articles identified, 88 were included (71 published and 17 unpublished). Data came from 26 countries; 62 studies (70%) were from high-income countries, and 58 studies (66%) were from programs only for men who have sex with men. In studies reporting a composite outcome of chlamydia, gonorrhea, and early syphilis, the pooled prevalence was 23.9% (95% CI, 18.6%-29.6%) before starting PrEP. The prevalence of the STI pathogen by anatomical site showed that prevalence was highest in the anorectum (chlamydia, 8.5% [95% CI, 6.3%-11.0%]; gonorrhea, 9.3% [95% CI, 4.7%-15.2%]) compared with genital sites (chlamydia, 4.0% [95% CI, 2.0%-6.6%]; gonorrhea, 2.1% [95% CI, 0.9%-3.7%]) and oropharyngeal sites (chlamydia, 2.4% [95% CI, 0.9%-4.5%]; gonorrhea, 4.9% [95% CI, 1.9%-9.1%]). The pooled incidence of studies reporting the composite outcome of chlamydia, gonorrhea, and early syphilis was 72.2 per 100 person-years (95% CI, 60.5-86.2 per 100 person-years). Conclusions and Relevance: Given the high burden of STIs among individuals initiating PrEP as well as persistent users of PrEP, this study highlights the need for active integration of HIV and STI services for an at-risk and underserved population.

Going global: the adoption of the World Health Organization's enabling recommendation on oral pre-exposure prophylaxis for HIV.

In September 2015, the World Health Organization (WHO) launched evidence-based guidelines by recommending that any person at substantial HIV risk should be offered oral pre-exposure prophylaxis (PrEP) containing tenofovir disoproxil fumarate (TDF) as an additional prevention choice. Since 2017, PrEP medicines have also been listed in the WHO's Essential Medicines List, including TDF/emtricitabine (FTC) and TDF in combination with lamivudine (3TC). A descriptive policy review and analysis of countries adopting WHO's 2015 recommendation on oral PrEP was conducted. As of June 2018, we identified 35 countries that had some type of policy on oral PrEP, and an additional five countries where a specific policy on PrEP is currently pending. A total of 19 high-income countries (HICs) and 21 low- and middle-income countries (LMICs) have adopted or have a pending policy. Most countries that have adopted or pending PrEP are in the European (42.9%) or African (30.0%) region. TDF/FTC is the most commonly recommended PrEP drug in the guidelines reviewed, although seven countries, namely in sub-Saharan Africa (6/7), are also recommending the use of TDF/3TC for PrEP. In sum, by the end of 2018, at least 40 countries (20.6%) are anticipated to have adopted WHO's oral PrEP recommendation. Nonetheless, policy uptake does not reflect broader programmatic coverage of PrEP services, which remain limited across all settings, irrespective of income status. Enhancing global partnerships is needed to support and track ongoing policy adoption and to ensure that policy is translated into meaningful implementation of PrEP services.

A Systematic Review of the Inclusion (or Exclusion) of Women in HIV Research: From Clinical Studies of Antiretrovirals and Vaccines to Cure Strategies.

INTRODUCTION: The effect of clinical interventions can differ because of sex/gender. Studies have shown that women are often under-represented in medical research. The aim of this systematic literature review was to characterize women's participation in HIV clinical studies of antiretroviral drugs (ARV), prophylactic vaccines (VAX), and curative strategies (CURE). METHODS: Systematic PubMed searches were conducted to identify ARV, VAX, and CURE studies. Data were extracted on the number of women, date of publication, sources of funding, country of study, and trial phase. Correlates of female participation were assessed. RESULTS: Women represented a median of 19.2% participants in ARV studies (387), 38.1% in VAX studies (53), and 11.1% in CURE studies (104). Funding source was not correlated with the proportion of female participants in VAX and CURE studies but was for ARV studies (P = 0.03). ARV trials funded by private noncommercial sources had the highest proportion of women, whereas publicly funded trials had the lowest female participation (median 16.7%). The median proportion of women in ARV trials that were fully or partially funded by the National Institutes of Health was significantly lower than the median in trials funded by other sources (19.6% vs. 22.3%, P = 0.001). CONCLUSIONS: Although women comprise nearly half of people living with HIV, they continue to be under-represented in clinical studies. Despite federal policies that have been established to address this, our study shows that publicly funded ARV trials recruit even fewer women than other trials. There is an urgent need to ensure that HIV clinical studies consider sex/gender dimensions.

Effectiveness and safety of oral HIV preexposure prophylaxis for all populations.

OBJECTIVE: Preexposure prophylaxis (PrEP) offers a promising new approach to HIV prevention. This systematic review and meta-analysis evaluated the evidence for use of oral PrEP containing tenofovir disoproxil fumarate as an additional HIV prevention strategy in populations at substantial risk for HIV based on HIV acquisition, adverse events, drug resistance, sexual behavior, and reproductive health outcomes. DESIGN: Rigorous systematic review and meta-analysis. METHODS: A comprehensive search strategy reviewed three electronic databases and conference abstracts through April 2015. Pooled effect estimates were calculated using random-effects meta-analysis. RESULTS: Eighteen studies were included, comprising data from 39 articles and six conference abstracts. Across populations and PrEP regimens, PrEP significantly reduced the risk of HIV acquisition compared with placebo. Trials with PrEP use more than 70% demonstrated the highest PrEP effectiveness (risk ratio = 0.30, 95% confidence interval: 0.21-0.45, P < 0.001) compared with placebo. Trials with low PrEP use did not show a significantly protective effect. Adverse events were similar between PrEP and placebo groups. More cases of drug-resistant HIV infection were found among PrEP users who initiated PrEP while acutely HIV-infected, but incidence of acquiring drug-resistant HIV during PrEP use was low. Studies consistently found no association between PrEP use and changes in sexual risk behavior. PrEP was not associated with increased pregnancy-related adverse events or hormonal contraception effectiveness. CONCLUSION: PrEP is protective against HIV infection across populations, presents few significant safety risks, and there is no evidence of behavioral risk compensation. The effective and cost-effective use of PrEP will require development of best practices for fostering uptake and adherence among people at substantial HIV risk.

An underestimated lentivirus model: what can HIV-2 research contribute to the development of an effective HIV-1 vaccine?

The development of an HIV-1 vaccine that would be effective against all existing subtypes and circulating recombinant forms remains one of the great scientific and public health challenges of our generation. One of the major barriers to HIV-1 vaccine development is a lack of understanding of the correlates of protective immunity against the virus. In this context, research has focused on the rare phenomenon of spontaneous control of HIV-1 infection, in groups referred to as 'long-term nonprogressors' and 'elite controllers', together with models of nonprogressive sooty mangabey simian immunodeficiency (SIV) infection in African nonhuman primate hosts such as sooty mangabeys and African green monkeys, in which the majority of animals tolerate high levels of viral replication without development of immunodeficiency or disease. Much less attention has been given to humans infected with the nonpandemic strain HIV-2, derived from the SIV in West Africa, most of whom behave as long-term nonprogressors or viral controllers, while a minority develop disease clinically indistinguishable from AIDS caused by HIV-1. This apparent dichotomous outcome is, based on the evidence accumulated to date, more clearly related to the host immune response than the good clinical outcome of HIV-1 controllers. We propose that complementing research into HIV-1 controllers and nonpathogenic SIV models with the prioritization of HIV-2 research could enhance the HIV-1 vaccine research effort. The absence of disease progression or detectable plasma viral replication in the presence of an effective immune response in most patients living with HIV-2 represents an opportunity to unravel the virus' evolutionary adaptation in human hosts and to establish the correlates of such a protective response.