Combination HIV Prevention among MSM in South Africa: Results from Agent-based Modeling

HIV prevention trials have demonstrated the effectiveness of a number of behavioral and biomedical interventions. HIV prevention packages are combinations of interventions and offer potential to significantly increase the effectiveness of any single intervention. Estimates of the effectiveness of prevention packages are important for guiding the development of prevention strategies and for characterizing effect sizes before embarking on large scale trials. Unfortunately, most research to date has focused on testing single interventions rather than HIV prevention packages. Here we report the results from agent-based modeling of the effectiveness of HIV prevention packages for men who have sex with men (MSM) in South Africa. We consider packages consisting of four components: antiretroviral therapy for HIV infected persons with CD4 count <350; PrEP for high risk uninfected persons; behavioral interventions to reduce rates of unprotected anal intercourse (UAI); and campaigns to increase HIV testing. We considered 163 HIV prevention packages corresponding to different intensity levels of the four components. We performed 2252 simulation runs of our agent-based model to evaluate those packages. We found that a four component package consisting of a 15% reduction in the rate of UAI, 50% PrEP coverage of high risk uninfected persons, 50% reduction in persons who never test for HIV, and 50% ART coverage over and above persons already receiving ART at baseline, could prevent 33.9% of infections over 5 years (95% confidence interval, 31.5, 36.3). The package components with the largest incremental prevention effects were UAI reduction and PrEP coverage. The impact of increased HIV testing was magnified in the presence of PrEP. We find that HIV prevention packages that include both behavioral and biomedical components can in combination prevent significant numbers of infections with levels of coverage, acceptance and adherence that are potentially achievable among MSM in South Africa.     

The impact of pre-exposure prophylaxis (PrEP) on HIV epidemics in Africa and India: a simulation study

Background

Pre-exposure prophylaxis (PrEP) is a promising new HIV prevention method, especially for women. An urgent demand for implementation of PrEP is expected at the moment efficacy has been demonstrated in clinical trials. We explored the long-term impact of PrEP on HIV transmission in different HIV epidemics.

Methodology/Principal Findings

We used a mathematical model that distinguishes the general population, sex workers and their clients. PrEP scenarios varying in effectiveness, coverage and target group were modeled in the epidemiological settings of Botswana, Nyanza Province in Kenya, and Southern India. We also studied the effect of condom addition or condom substitution during PrEP use. Main outcome was number of HIV infections averted over ten years of PrEP use. PrEP strategies with high effectiveness and high coverage can have a substantial impact in African settings. In Southern India, by contrast, the number of averted HIV infections in different PrEP scenarios would be much lower. The impact of PrEP may be strongly diminished or even reversed by behavioral disinhibition, especially in scenarios with low coverage and low effectiveness. However, additional condom use during low coverage and low effective PrEP doubled the amount of averted HIV infections.

Conclusions/Significance

The public health impact of PrEP can be substantial. However, this impact may be diminished, or even reversed, by changes in risk behavior. Implementation of PrEP strategies should therefore come on top of current condom campaigns, not as a substitution.     

The Potential Impact of Pre-Exposure Prophylaxis for HIV Prevention among Men Who Have Sex with Men and Transwomen in Lima, Peru: A Mathematical Modelling Study

Background

HIV pre-exposure prophylaxis (PrEP), the use of antiretroviral drugs by uninfected individuals to prevent HIV infection, has demonstrated effectiveness in preventing acquisition in a high-risk population of men who have sex with men (MSM). Consequently, there is a need to understand if and how PrEP can be used cost-effectively to prevent HIV infection in such populations.

Methods and Findings

We developed a mathematical model representing the HIV epidemic among MSM and transwomen (male-to-female transgender individuals) in Lima, Peru, as a test case. PrEP effectiveness in the model is assumed to result from the combination of a “conditional efficacy” parameter and an adherence parameter. Annual operating costs from a health provider perspective were based on the US Centers for Disease Control and Prevention interim guidelines for PrEP use. The model was used to investigate the population-level impact, cost, and cost-effectiveness of PrEP under a range of implementation scenarios. The epidemiological impact of PrEP is largely driven by programme characteristics. For a modest PrEP coverage of 5%, over 8% of infections could be averted in a programme prioritising those at higher risk and attaining the adherence levels of the Pre-Exposure Prophylaxis Initiative study. Across all scenarios, the highest estimated cost per disability-adjusted life year averted (uniform strategy for a coverage level of 20%, US$1,036–US$4,254) is below the World Health Organization recommended threshold for cost-effective interventions, while only certain optimistic scenarios (low coverage of 5% and some or high prioritisation) are likely to be cost-effective using the World Bank threshold. The impact of PrEP is reduced if those on PrEP decrease condom use, but only extreme behaviour changes among non-adherers (over 80% reduction in condom use) and a low PrEP conditional efficacy (40%) would adversely impact the epidemic. However, PrEP will not arrest HIV transmission in isolation because of its incomplete effectiveness and dependence on adherence, and because the high cost of programmes limits the coverage levels that could potentially be attained.

Conclusions

A strategic PrEP intervention could be a cost-effective addition to existing HIV prevention strategies for MSM populations. However, despite being cost-effective, a substantial expenditure would be required to generate significant reductions in incidence. Please see later in the article for the Editors'' Summary     

Integrated Delivery of Antiretroviral Treatment and Pre-exposure Prophylaxis to HIV-1–Serodiscordant Couples: A Prospective Implementation Study in Kenya and Uganda

BackgroundAntiretroviral-based interventions for HIV-1 prevention, including antiretroviral therapy (ART) to reduce the infectiousness of HIV-1 infected persons and pre-exposure prophylaxis (PrEP) to reduce the susceptibility of HIV-1 uninfected persons, showed high efficacy for HIV-1 protection in randomized clinical trials. We conducted a prospective implementation study to understand the feasibility and effectiveness of these interventions in delivery settings.ConclusionsIntegrated delivery of time-limited PrEP until sustained ART use in African HIV-1-serodiscordant couples was feasible, demonstrated high uptake and adherence, and resulted in near elimination of HIV-1 transmission, with an observed HIV incidence of <0.5% per year compared to an expected incidence of >5% per year.     

Analytic Review of Modeling Studies of ARV Based PrEP Interventions Reveals Strong Influence of Drug-Resistance Assumptions on the Population-Level Effectiveness

Background

Four clinical trials have shown that oral and topical pre-exposure prophylaxis (PrEP) based on tenofovir may be effective in preventing HIV transmission. The expected reduction in HIV transmission and the projected prevalence of drug resistance due to PrEP use vary significantly across modeling studies as a result of the broad spectrum of assumptions employed. Our goal is to quantify the influence of drug resistance assumptions on the predicted population-level impact of PrEP.

Methods

All modeling studies which evaluate the impact of oral or topical PrEP are reviewed and key assumptions regarding mechanisms of generation and spread of drug-resistant HIV are identified. A dynamic model of the HIV epidemic is developed to assess and compare the impact of oral PrEP using resistance assumptions extracted from published studies. The benefits and risks associated with ten years of PrEP use are evaluated under identical epidemic, behavioral and intervention conditions in terms of cumulative fractions of new HIV infections prevented, resistance prevalence among those infected with HIV, and fractions of infections in which resistance is transmitted.

Results

Published models demonstrate enormous variability in resistance-generating assumptions and uncertainty in parameter values. Depending on which resistance parameterization is used, a resistance prevalence between 2% and 44% may be expected if 50% efficacious oral PrEP is used consistently by 50% of the population over ten years. We estimated that resistance may be responsible for up to a 10% reduction or up to a 30% contribution to the fraction of prevented infections predicted in different studies.

Conclusions

Resistance assumptions used in published studies have a strong influence on the projected impact of PrEP. Modelers and virologists should collaborate toward clarifying the set of resistance assumptions biologically relevant to the PrEP products which are already in use or soon to be added to the arsenal against HIV.     

Because we can: clashes of perspective over researcher obligation in the failed PrEP trials

This article examines the relationship between bioethics and the therapeutic standards in HIV prevention research in the developing world, focusing on the closure of the pre-exposure prophylaxis (PrEP) trials in the early 2000s. I situate the PrEP trials in the historical context of the vertical transmission debates of the 1990s, where there was protracted debate over the use of placebos despite the existence of a proven intervention. I then discuss the dramatic improvement in the clinical management of HIV and the treatment access movement, and consider how these contexts have influenced research practice. I argue that as HIV prevention trials oblige researchers to observe the rate at which vulnerable people under their care acquire HIV, there is an obligation to provide antiretroviral treatment to seroconverters and other health care benefits that fall within the scope of researchers' entrustment, both to avoid exploitation and to enact reciprocal justice. I argue against propositions that the obligations to provide specific benefits are vague, fall only upon researchers and sponsors, and create injustices by privileging the few over the many. Finally, I contend that the realisation of a broader standard of care in HIV prevention research broadens the role of research from being a simple tool to produce knowledge to a complex intervention that can play a part in the reduction of health disparities.     

Knowledge,Indications and Willingness to Take Pre-Exposure Prophylaxis among Transwomen in San Francisco, 2013

Safe and effective HIV prevention strategies are needed for transwomen. Transwomen in the US have a 34 times greater odds of being infected with HIV than all adults age 15-49, and in San Francisco, California 42.4% of transwomen are estimated to be infected with HIV. Pre-exposure prophylaxis (PrEP) is the first biomedical intervention with promise for reducing HIV acquisition in transwomen. However, little is known about whether transwomen know about PrEP, are taking PrEP and would be good candidates for PrEP based on their risk profile and behaviors. A population-based dataset was analyzed to determine how many transwomen in San Francisco knew about PrEP by the end of 2013 – more than a year after iPrex results demonstrated efficacy of PrEP in preventing HIV. We found that of 233 transwomen, only 13.7% had heard of PrEP. Transwomen who were living with HIV compared to those who were HIV-negative, and those who recently injected drugs compared to non-injection drug users were more likely to have heard of PrEP. Based on CDC guidelines for PrEP among MSM and IDU, 45 (30.2%) transwomen of the 149 HIV-negative transwomen in the sample were candidates for PrEP. This estimate based on CDC criteria is arguably low. Given that almost half of transwomen in San Francisco are living with HIV, this findings points to a need for further consideration of PrEP criteria that are specific and tailored to the risks for HIV faced by transwomen that are different from MSM and injection drug users. Research to scale up access and test the effectiveness of PrEP for transwomen is also urgently needed.     

“How I Wish This Thing Was Initiated 100 Years Ago!” Willingness to Take Daily Oral Pre-Exposure Prophylaxis among Men Who Have Sex with Men in Kenya

BackgroundThe MSM population in Kenya contributes to 15% of HIV incidence. This calls for innovative HIV prevention interventions. Pre-exposure prophylaxis (PrEP) has been efficacious in preventing HIV among MSM in trials. There is limited data on the willingness to take daily oral PrEP in sub-Sahara Africa. PrEP has not been approved for routine use in most countries globally. This study aimed to document the willingness to take PrEP and barriers to uptake and adherence to PrEP in Kenya. The findings will inform the design of a PrEP delivery program as part of the routine HIV combination prevention.MethodsEighty MSM were recruited in 2 Counties in December 2013. Quantitative data on sexual behaviour and willingness to take PrEP were collected using semi-structured interviews and analysed using SPSS. Qualitative data on knowledge of PrEP, motivators and barriers to uptake and adherence to PrEP were collected using in-depth interviews and FGDs and analysed using Nvivo. Analysis of data in willingness to take PrEP was conducted on the HIV negative participants (n = 55).Results83% of MSM were willing to take daily oral HIV PrEP. Willingness to take PrEP was higher among the bi-sexual and younger men. Motivators for taking PrEP were the need to stay HIV negative and to protect their partners. History of poor medication adherence, fear of side effects and HIV stigma were identified as potential barriers to adherence. Participants were willing to buy PrEP at a subsidized price.ConclusionsThere is willingness to take PrEP among MSM in Kenya and there is need to invest in targeted education and messaging on PrEP to enhance adherence, proper use and reduce stigma in the general population and among policy makers.     

Effectiveness and Cost Effectiveness of Oral Pre-Exposure Prophylaxis in a Portfolio of Prevention Programs for Injection Drug Users in Mixed HIV Epidemics

Background

Pre-exposure prophylaxis with oral antiretroviral treatment (oral PrEP) for HIV-uninfected injection drug users (IDUs) is potentially useful in controlling HIV epidemics with a significant injection drug use component. We estimated the effectiveness and cost effectiveness of strategies for using oral PrEP in various combinations with methadone maintenance treatment (MMT) and antiretroviral treatment (ART) in Ukraine, a representative case for mixed HIV epidemics.

Methods and Findings

We developed a dynamic compartmental model of the HIV epidemic in a population of non-IDUs, IDUs who inject opiates, and IDUs in MMT, adding an oral PrEP program (tenofovir/emtricitabine, 49% susceptibility reduction) for uninfected IDUs. We analyzed intervention portfolios consisting of oral PrEP (25% or 50% of uninfected IDUs), MMT (25% of IDUs), and ART (80% of all eligible patients). We measured health care costs, quality-adjusted life years (QALYs), HIV prevalence, HIV infections averted, and incremental cost effectiveness. A combination of PrEP for 50% of IDUs and MMT lowered HIV prevalence the most in both IDUs and the general population. ART combined with MMT and PrEP (50% access) averted the most infections (14,267). For a PrEP cost of $950, the most cost-effective strategy was MMT, at $520/QALY gained versus no intervention. The next most cost-effective strategy consisted of MMT and ART, costing $1,000/QALY gained compared to MMT alone. Further adding PrEP (25% access) was also cost effective by World Health Organization standards, at $1,700/QALY gained. PrEP alone became as cost effective as MMT at a cost of $650, and cost saving at $370 or less.

Conclusions

Oral PrEP for IDUs can be part of an effective and cost-effective strategy to control HIV in regions where injection drug use is a significant driver of the epidemic. Where budgets are limited, focusing on MMT and ART access should be the priority, unless PrEP has low cost.     

Factors influencing the emergence and spread of HIV drug resistance arising from rollout of antiretroviral pre-exposure prophylaxis (PrEP)

Background

The potential for emergence and spread of HIV drug resistance from rollout of antiretroviral (ARV) pre-exposure prophylaxis (PrEP) is an important public health concern. We investigated determinants of HIV drug resistance prevalence after PrEP implementation through mathematical modeling.

Methodology

A model incorporating heterogeneity in age, gender, sexual activity, HIV infection status, stage of disease, PrEP coverage/discontinuation, and HIV drug susceptibility, was designed to simulate the impact of PrEP on HIV prevention and drug resistance in a sub-Saharan epidemic.

Principal Findings

Analyses suggest that the prevalence of HIV drug resistance is influenced most by the extent and duration of inadvertent PrEP use in individuals already infected with HIV. Other key factors affecting drug resistance prevalence include the persistence time of transmitted resistance and the duration of inadvertent PrEP use in individuals who become infected on PrEP. From uncertainty analysis, the median overall prevalence of drug resistance at 10 years was predicted to be 9.2% (interquartile range 6.9%–12.2%). An optimistic scenario of 75% PrEP efficacy, 60% coverage of the susceptible population, and 5% inadvertent PrEP use predicts a rise in HIV drug resistance prevalence to only 2.5% after 10 years. By contrast, in a pessimistic scenario of 25% PrEP efficacy, 15% population coverage, and 25% inadvertent PrEP use, resistance prevalence increased to over 40%.

Conclusions

Inadvertent PrEP use in previously-infected individuals is the major determinant of HIV drug resistance prevalence arising from PrEP. Both the rate and duration of inadvertent PrEP use are key factors. PrEP rollout programs should include routine monitoring of HIV infection status to limit the spread of drug resistance.     

Modeling the population-level effects of male circumcision as an HIV-preventive measure: a gendered perspective

Background

Evidence from biological, epidemiological, and controlled intervention studies has demonstrated that male circumcision (MC) protects males from HIV infection, and MC is now advocated as a public-health intervention against HIV. MC provides direct protection only to men, but is expected to provide indirect protection to women at risk of acquiring HIV from heterosexual transmission. How such indirect protection interacts with the possibility that MC campaigns will lead to behavior changes, however, is not yet well understood. Our objective here is to investigate the link between individual-level effects of MC campaigns and long-term population-level outcomes resulting from disease dynamics, looking at both genders separately, over a broad range of parameters.

Methods and Findings

We use simple mathematical models of heterosexual transmission to investigate the potential effects of a circumcision scale-up, combined with possible associated behavioral disinhibition. We examine patterns in expected long-term prevalence using a simple equilibrium model based on transmission factors, and validate our results with ODE-based simulations, focusing on the link between effects on females and those on males.We find that the long-term population-level effects on females and males are not strongly linked: there are many possible ways in which an intervention which reduces prevalence in males might nonetheless increase prevalence in females.

Conclusions

Since an intervention that reduces long-term male prevalence could nonetheless increase long-term female prevalence, MC campaigns should explicitly consider both the short-term and long-term effects of MC interventions on females. Our findings strongly underline the importance of pairing MC programs with education, support programs and HIV testing and counseling, together with other prevention measures.     

Optimal uses of antiretrovirals for prevention in HIV-1 serodiscordant heterosexual couples in South Africa: a modelling study

Background

Antiretrovirals have substantial promise for HIV-1 prevention, either as antiretroviral treatment (ART) for HIV-1–infected persons to reduce infectiousness, or as pre-exposure prophylaxis (PrEP) for HIV-1–uninfected persons to reduce the possibility of infection with HIV-1. HIV-1 serodiscordant couples in long-term partnerships (one member is infected and the other is uninfected) are a priority for prevention interventions. Earlier ART and PrEP might both reduce HIV-1 transmission in this group, but the merits and synergies of these different approaches have not been analyzed.

Methods and Findings

We constructed a mathematical model to examine the impact and cost-effectiveness of different strategies, including earlier initiation of ART and/or PrEP, for HIV-1 prevention for serodiscordant couples. Although the cost of PrEP is high, the cost per infection averted is significantly offset by future savings in lifelong treatment, especially among couples with multiple partners, low condom use, and a high risk of transmission. In some situations, highly effective PrEP could be cost-saving overall. To keep couples alive and without a new infection, providing PrEP to the uninfected partner could be at least as cost-effective as initiating ART earlier in the infected partner, if the annual cost of PrEP is <40% of the annual cost of ART and PrEP is >70% effective.

Conclusions

Strategic use of PrEP and ART could substantially and cost-effectively reduce HIV-1 transmission in HIV-1 serodiscordant couples. New and forthcoming data on the efficacy of PrEP, the cost of delivery of ART and PrEP, and couples behaviours and preferences will be critical for optimizing the use of antiretrovirals for HIV-1 prevention. Please see later in the article for the Editors'' Summary     

Integration of Social,Cultural, and Biomedical Strategies into an Existing Couple-Based Behavioral HIV/STI Prevention Intervention: Voices of Latino Male Couples

Introduction

Successful HIV prevention and treatment requires evidence-based approaches that combine biomedical strategies with behavioral interventions that are socially and culturally appropriate for the population or community being prioritized. Although there has been a push for a combination approach, how best to integrate different strategies into existing behavioral HIV prevention interventions remains unclear. The need to develop effective combination approaches is of particular importance for men who have sex with men (MSM), who face a disproportionately high risk of HIV acquisition.

Materials and Methods

We collaborated with Latino male couples and providers to adapt Connect ‘n Unite, an evidence-based intervention for Black male couples, for Latino male couples. We conducted a series of three focus groups, each with two cohorts of couples, and one focus group with providers. A purposive stratified sample of 20 couples (N = 40, divided into two cohorts) and 10 providers provided insights into how to adapt and integrate social, cultural, and biomedical approaches in a couples-based HIV/AIDS behavioral intervention.

Results

The majority (N = 37) of the couple participants had no prior knowledge of the following new biomedical strategies: non-occupational post-exposure prophylaxis (nPEP); pre-exposure prophylaxis (PrEP); and HIV self-testing kits. After they were introduced to these biomedical interventions, all participants expressed a need for information and empowerment through knowledge and awareness of these interventions. In particular, participants suggested that we provide PrEP and HIV self-testing kits by the middle or end of the intervention. Providers suggested a need to address behavioral, social and structural issues, such as language barriers; and the promotion of client-centered approaches to increase access to, adaptation of, and adherence to biomedical strategies. Corroborating what couple participants suggested, providers agreed that biomedical strategies should be offered after providing information about these tools. Regarding culturally sensitive and responsive approaches, participants identified stigma and discrimination associated with HIV and sexual identity as barriers to care, language barriers and documentation status as further barriers to care, the couple-based approach as ideal to health promotion, and the need to include family topics in the intervention.

Discussion

We successfully adapted an evidence-based behavioral HIV prevention intervention for Latino male couples. The adapted intervention, called Conectando Latinos en Pareja, integrates social, cultural, behavioral and biomedical strategies to address the HIV epidemic among Latino MSM. The study highlights the promise regarding the feasibility of implementing a combination approach to HIV prevention in this population.     

Client and Provider Perspectives on New HIV Prevention Tools for MSM in the Americas

Men who have sex with men (MSM) in the Americas require targeted, combination HIV prevention approaches. We solicited client and provider perspectives on emerging prevention interventions including HIV pre-exposure prophylaxis (PrEP) and HIV self-tests through focus groups and in-depth interviews with 130 MSM and 41 providers across four sites: New York, San Francisco, Lima, and Rio de Janeiro. Among the MSM participants, we identified three prevention typologies: non-condom users, inconsistent condom users, and consistent condom users. Northern and Southern MSM differed in the variety of harm reduction strategies utilized: where U.S. MSM relied on condom use as well as disclosure and seroadaptive behaviors for prevention, condom use without disclosure or serostatus discussions was the norm in South America. Interest in new prevention technologies was shaped by the social context. U.S. MSM preferences differed by typology, such that non-condom users were interested in taking PrEP and using home HIV tests. MSM in Brazil, regardless of typology, were interested in exploring new prevention options. MSM in Peru demonstrated moderate interest but were less comfortable with adopting new strategies. MSM and providers’ opinions differed substantially with respect to new prevention options. Across sites, most providers were reticent to engage with new prevention options, though some NGO-based providers were more supportive of exploring new prevention tools. Both clients and providers will need to be engaged in developing integrated prevention strategies for MSM.     

Clinical Effectiveness and Cost-Effectiveness of HIV Pre-Exposure Prophylaxis in Men Who Have Sex with Men: Risk Calculators for Real-World Decision-Making

Background

Oral pre-exposure prophylaxis (PrEP) can be clinically effective and cost-effective for HIV prevention in high-risk men who have sex with men (MSM). However, individual patients have different risk profiles, real-world populations vary, and no practical tools exist to guide clinical decisions or public health strategies. We introduce a practical model of HIV acquisition, including both a personalized risk calculator for clinical management and a cost-effectiveness calculator for population-level decisions.

Methods

We developed a decision-analytic model of PrEP for MSM. The primary clinical effectiveness and cost-effectiveness outcomes were the number needed to treat (NNT) to prevent one HIV infection, and the cost per quality-adjusted life-year (QALY) gained. We characterized patients according to risk factors including PrEP adherence, condom use, sexual frequency, background HIV prevalence and antiretroviral therapy use.

Results

With standard PrEP adherence and national epidemiologic parameters, the estimated NNT was 64 (95% uncertainty range: 26, 176) at a cost of $160,000 (cost saving, $740,000) per QALY – comparable to other published models. With high (35%) HIV prevalence, the NNT was 35 (21, 57), and cost per QALY was $27,000 (cost saving, $160,000), and with high PrEP adherence, the NNT was 30 (14, 69), and cost per QALY was $3,000 (cost saving, $200,000). In contrast, for monogamous, serodiscordant relationships with partner antiretroviral therapy use, the NNT was 90 (39, 157) and cost per QALY was $280,000 ($14,000, $670,000).

Conclusions

PrEP results vary widely across individuals and populations. Risk calculators may aid in patient education, clinical decision-making, and cost-effectiveness evaluation.     

Prevention of rectal SHIV transmission in macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir

Background

In the absence of an effective vaccine, HIV continues to spread globally, emphasizing the need for novel strategies to limit its transmission. Pre-exposure prophylaxis (PrEP) with antiretroviral drugs could prove to be an effective intervention strategy if highly efficacious and cost-effective PrEP modalities are identified. We evaluated daily and intermittent PrEP regimens of increasing antiviral activity in a macaque model that closely resembles human transmission.

Methods and Findings

We used a repeat-exposure macaque model with 14 weekly rectal virus challenges. Three drug treatments were given once daily, each to a different group of six rhesus macaques. Group 1 was treated subcutaneously with a human-equivalent dose of emtricitabine (FTC), group 2 received orally the human-equivalent dosing of both FTC and tenofovir-disoproxil fumarate (TDF), and group 3 received subcutaneously a similar dosing of FTC and a higher dose of tenofovir. A fourth group of six rhesus macaques (group 4) received intermittently a PrEP regimen similar to group 3 only 2 h before and 24 h after each weekly virus challenge. Results were compared to 18 control macaques that did not receive any drug treatment. The risk of infection in macaques treated in groups 1 and 2 was 3.8- and 7.8-fold lower than in untreated macaques (p = 0.02 and p = 0.008, respectively). All six macaques in group 3 were protected. Breakthrough infections had blunted acute viremias; drug resistance was seen in two of six animals. All six animals in group 4 that received intermittent PrEP were protected.

Conclusions

This model suggests that single drugs for daily PrEP can be protective but a combination of antiretroviral drugs may be required to increase the level of protection. Short but potent intermittent PrEP can provide protection comparable to that of daily PrEP in this SHIV/macaque model. These findings support PrEP trials for HIV prevention in humans and identify promising PrEP modalities.     

Frequency of False Positive Rapid HIV Serologic Tests in African Men and Women Receiving PrEP for HIV Prevention: Implications for Programmatic Roll-Out of Biomedical Interventions

Background

Rapid HIV assays are the mainstay of HIV testing globally. Delivery of effective biomedical HIV prevention strategies such as antiretroviral pre-exposure prophylaxis (PrEP) requires periodic HIV testing. Because rapid tests have high (>95%) but imperfect specificity, they are expected to generate some false positive results.

Methods

We assessed the frequency of true and false positive rapid results in the Partners PrEP Study, a randomized, placebo-controlled trial of PrEP. HIV testing was performed monthly using 2 rapid tests done in parallel with HIV enzyme immunoassay (EIA) confirmation following all positive rapid tests.

Results

A total of 99,009 monthly HIV tests were performed; 98,743 (99.7%) were dual-rapid HIV negative. Of the 266 visits with ≥1 positive rapid result, 99 (37.2%) had confirmatory positive EIA results (true positives), 155 (58.3%) had negative EIA results (false positives), and 12 (4.5%) had discordant EIA results. In the active PrEP arms, over two-thirds of visits with positive rapid test results were false positive results (69.2%, 110 of 159), although false positive results occurred at <1% (110/65,945) of total visits.

Conclusions

When HIV prevalence or incidence is low due to effective HIV prevention interventions, rapid HIV tests result in a high number of false relative to true positive results, although the absolute number of false results will be low. Program roll-out for effective interventions should plan for quality assurance of HIV testing, mechanisms for confirmatory HIV testing, and counseling strategies for persons with positive rapid test results.