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.     

Complex and Conflicting Social Norms: Implications for Implementation of Future HIV Pre-Exposure Prophylaxis (PrEP) Interventions in Vancouver,Canada

Background

HIV Pre-Exposure Prophylaxis (PrEP) has been found to be efficacious in preventing HIV acquisition among seronegative individuals in a variety of risk groups, including men who have sex with men and people who inject drugs. To date, however, it remains unclear how socio-cultural norms (e.g., attitudes towards HIV; social understandings regarding HIV risk practices) may influence the scalability of future PrEP interventions. The objective of this study is to assess how socio-cultural norms may influence the implementation and scalability of future HIV PrEP interventions in Vancouver, Canada.

Methods

We conducted 50 interviews with young men (ages 18–24) with a variety of HIV risk behavioural profiles (e.g., young men who inject drugs; MSM). Interviews focused on participants’ experiences and perceptions with various HIV interventions and policies, including PrEP.

Results

While awareness of PrEP was generally low, perceptions about the potential personal and public health gains associated with PrEP were interconnected with expressions of complex and sometimes conflicting social norms. Some accounts characterized PrEP as a convenient form of reliable protection against HIV, likening it to the female birth control pill. Other accounts cast PrEP as a means to facilitate ‘socially unacceptable’ behaviour (e.g., promiscuity). Stigmatizing rhetoric was used to position PrEP as a tool that could promote some groups’ proclivities to take ‘risks’.

Conclusion

Stigma regarding ‘risky’ behaviour and PrEP should not be underestimated as a serious implementation challenge. Pre-implementation strategies that concomitantly aim to improve knowledge about PrEP, while addressing associated social prejudices, may be key to effective implementation and scale-up.     

Knowledge,Attitudes, and Acceptability of Pre-Exposure Prophylaxis among Individuals Living with HIV in an Urban HIV Clinic

Introduction

Pre-exposure prophylaxis (PrEP) is an effective tool to reduce HIV transmission. The primary objective of this study was to assess awareness of PrEP by individuals living with HIV (HIV+) and acceptance of its use for their HIV negative (HIV-) partners.

Methods

A cross sectional survey was conducted among individuals living with HIV who received care at an urban HIV clinic between January 2013 and June 2013. The survey examined knowledge, attitudes, and acceptability of PrEP, and perception of transmission risk of HIV. Chi-Square test and Fisher''s Exact test were used to compare proportions.

Results

Among 206 subjects living with HIV, 15.3% (32) had heard of PrEP. Men who have sex with men (MSM) were more likely to be aware of PrEP than all others (p = 0.003). Once educated about PrEP those who believed PrEP would reduce their partner’s risk for HIV were more likely to recommend PrEP to their partner (p<0.001). 92% of all respondents said they would be “extremely likely/likely” to discuss PrEP use with their provider. Of 159 subjects whose main partner was HIV-, MSM (p = 0.007), male participants (p = 0.044), and those who were consistently taking meds (p = 0.049) were more likely to be aware of PrEP. Those who perceived they were at risk of transmitting HIV (p<0.001) and those who were consistently taking meds (0.049) were more likely to agree that PrEP could reduce the risk of HIV to their partners.

Conclusion

This study illustrates a low awareness of PrEP but once educated the willingness of a cohort of individuals living with HIV to recommend PrEP to their partners. Our findings demonstrate the importance of providers informing their patients living with HIV about PrEP, as these persons are an underutilized link to support the uptake of PrEP by their HIV- partners.     

Acceptability of Using Electronic Vending Machines to Deliver Oral Rapid HIV Self-Testing Kits: A Qualitative Study

Introduction

Rates of unrecognized HIV infection are significantly higher among Latino and Black men who have sex with men (MSM). Policy makers have proposed that HIV self-testing kits and new methods for delivering self-testing could improve testing uptake among minority MSM. This study sought to conduct qualitative assessments with MSM of color to determine the acceptability of using electronic vending machines to dispense HIV self-testing kits.

Materials and Methods

African American and Latino MSM were recruited using a participant pool from an existing HIV prevention trial on Facebook. If participants expressed interest in using a vending machine to receive an HIV self-testing kit, they were emailed a 4-digit personal identification number (PIN) code to retrieve the test from the machine. We followed up with those who had tested to assess their willingness to participate in an interview about their experience.

Results

Twelve kits were dispensed and 8 interviews were conducted. In general, participants expressed that the vending machine was an acceptable HIV test delivery method due to its novelty and convenience.

Discussion

Acceptability of this delivery model for HIV testing kits was closely associated with three main factors: credibility, confidentiality, and convenience. Future research is needed to address issues, such as user-induced errors and costs, before scaling up the dispensing method.     

Awareness of and Willingness to Use Oral Pre-Exposure Prophylaxis for HIV Prevention among HIV-Serodiscordant Heterosexual Couples: A Cross-Sectional Survey in Xinjiang,China

Objectives

We aimed to investigate the awareness of and willingness to use oral pre-exposure prophylaxis (PrEP) for HIV prevention among HIV-negative partners in HIV-serodiscordant heterosexual couples in Xinjiang, China and determine factors that predict willingness to use oral PrEP.

Methods

Between November 2009 and December 2010, a cross-sectional survey was carried out among 351 HIV-negative partners in HIV-serodiscordant heterosexual couples from three cities in Xinjiang, China. Participants completed a self-administered questionnaire to assess their awareness of and willingness to use oral PrEP. Additionally, blood samples were collected to test for HIV infection. Univariate and multivariate logistic regression analyses were performed to identify predictors of willingness to use oral PrEP.

Results

Only 10 participants (2.8%) reported having heard of PrEP, and only two reported ever using PrEP. However, 297 (84.6%) reported that they were willing to use oral PrEP if it was proven to be both safe and effective. Results of multivariate analysis revealed the following independent predictors of willingness to use oral PrEP: monthly household income (adjusted odds ratio = 2.78, <1000 RMB vs. ≥1000 RMB, 95% confidence interval: 1.36–5.69), perceived likelihood of contracting HIV from HIV-positive partner (adjusted odds ratio = 2.63, likely vs. unlikely, 95% confidence interval: 1.12–6.19), and worrying about being discriminated against by others due to oral PrEP use (adjusted odds ratio  = 9.43, No vs. Yes, 95% confidence interval: 3.78–23.50).

Conclusions

Our results showed HIV-negative partners in HIV-serodiscordant heterosexual couples in China had low awareness of oral PrEP but high willingness to use oral PrEP for HIV prevention. Cost of oral PrEP should be taken into consideration in future PrEP prevention strategy. In addition, efforts should be made to reduce stigma attached to oral PrEP use, which may increase its acceptability among potential users.     

Evolving Strategies, Opportunistic Implementation: HIV Risk Reduction in Tanzania in the Context of an Incentive-Based HIV Prevention Intervention

Background

Behavior change communication (BCC) interventions, while still a necessary component of HIV prevention, have not on their own been shown to be sufficient to stem the tide of the epidemic. The shortcomings of BCC interventions are partly due to barriers arising from structural or economic constraints. Arguments are being made for combination prevention packages that include behavior change, biomedical, and structural interventions to address the complex set of risk factors that may lead to HIV infection.

Methods

In 2009/2010 we conducted 216 in-depth interviews with a subset of study participants enrolled in the RESPECT study - an HIV prevention trial in Tanzania that used cash awards to incentivize safer sexual behaviors. We analyzed community diaries to understand how the study was perceived in the community. We drew on these data to enhance our understanding of how the intervention influenced strategies for risk reduction.

Results

We found that certain situations provide increased leverage for sexual negotiation, and these situations facilitated opportunistic implementation of risk reduction strategies. Opportunities enabled by the RESPECT intervention included leveraging conditional cash awards, but participants also emphasized the importance of exploiting new health status knowledge from regular STI testing. Risk reduction strategies included condom use within partnerships and/or with other partners, and an unexpected emphasis on temporary abstinence.

Conclusions

Our results highlight the importance of increasing opportunities for implementing risk reduction strategies. We found that an incentive-based intervention could be effective in part by creating such opportunities, particularly among groups such as women with limited sexual agency. The results provide new evidence that expanding regular testing of STIs is another important mechanism for providing opportunities for negotiating behavior change, beyond the direct benefits of testing. Exploiting the latent demand for STI testing should receive renewed attention as part of innovative new combination interventions for HIV prevention.     

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     

Estimating the Cost-Effectiveness of Pre-Exposure Prophylaxis to Reduce HIV-1 and HSV-2 Incidence in HIV-Serodiscordant Couples in South Africa

Objective

To estimate the cost-effectiveness of daily oral tenofovir-based PrEP, with a protective effect against HSV-2 as well as HIV-1, among HIV-1 serodiscordant couples in South Africa.

Methods

We incorporated HSV-2 acquisition, transmission, and interaction with HIV-1 into a microsimulation model of heterosexual HIV-1 serodiscordant couples in South Africa, with use of PrEP for the HIV-1 uninfected partner prior to ART initiation for the HIV-1 1infected partner, and for one year thereafter.

Results

We estimate the cost per disability-adjusted life-year (DALY) averted for two scenarios, one in which PrEP has no effect on reducing HSV-2 acquisition, and one in which there is a 33% reduction. After a twenty-year intervention, the cost per DALY averted is estimated to be $10,383 and $9,757, respectively – a 6% reduction, given the additional benefit of reduced HSV-2 acquisition. If all couples are discordant for both HIV-1 and HSV-2, the cost per DALY averted falls to $1,445, which shows that the impact is limited by HSV-2 concordance in couples.

Conclusion

After a 20-year PrEP intervention, the cost per DALY averted with a reduction in HSV-2 is estimated to be modestly lower than without any effect, providing an increase of health benefits in addition to HIV-1 prevention at no extra cost. The small degree of the effect is in part due to a high prevalence of HSV-2 infection in HIV-1 serodiscordant couples in South Africa.     

Preparing for the Rollout of Pre-Exposure Prophylaxis (PrEP): A Vignette Survey to Identify Intended Sexual Behaviors among Women in Kenya and South Africa if Using PrEP

Introduction

Several clinical trials have demonstrated the efficacy of pre-exposure prophylaxis (PrEP) in reducing HIV risk. One concern with introducing PrEP is whether users will engage in riskier sexual behaviors.

Methods

We assessed the effect that PrEP may have on sexual risk behaviors by administering a survey to 799 women in Bondo, Kenya, and Pretoria, South Africa. Participants were asked about their sexual behavior intentions twice — once as if they were taking PrEP and once as if they were not taking PrEP — within four risk situations (vignettes). They responded using a 5-point ordinal scale. We used a series of linear mixed effects models with an unstructured residual covariance matrix to estimate the between- and within-subject differences in the mean likelihood of engaging in risky sexual behavior across the PrEP and non-PrEP contexts. We also calculated the total percentage of participants who reported a greater likelihood of engaging in risky sexual behavior if taking PrEP than if not taking PrEP, by vignette.

Results

We found statistically significant differences in the mean likelihood of engaging in risky sexual behavior with the between-subject comparison (-0.17, p < 0.01) and with the within-subject comparison (-0.31, p < 0.001). Depending on the vignette, 27% to 40% of participants reported a greater likelihood of engaging in risky sexual behavior if taking PrEP than if not taking PrEP.

Conclusions

Our findings indicate that modest increases in risky sexual behavior could occur with PrEP. Although responses from the majority of participants suggest they would not be more likely to engage in risky sexual behavior if they took PrEP, a substantial proportion might. Programs rolling out PrEP should be prepared to assist similar women in making informed choices about reducing their risk of HIV and about their sexual health beyond HIV prevention.     

Access to Healthcare,HIV/STI Testing,and Preferred Pre-Exposure Prophylaxis Providers among Men Who Have Sex with Men and Men Who Engage in Street-Based Sex Work in the US

Background

Pre-exposure prophylaxis (PrEP) is a promising strategy for HIV prevention among men who have sex with men (MSM) and men who engage in sex work. But access will require routine HIV testing and contacts with healthcare providers. This study investigated men’s healthcare and HIV testing experiences to inform PrEP implementation.

Methods

We conducted 8 focus groups (n = 38) in 2012 and 56 in-depth qualitative interviews in 2013–14 with male sex workers (MSWs) (n = 31) and other MSM (n = 25) in Providence, RI. MSWs primarily met clients in street-based sex work venues. Facilitators asked participants about access to healthcare and HIV/STI testing, healthcare needs, and preferred PrEP providers.

Results

MSWs primarily accessed care in emergency rooms (ERs), substance use clinics, correctional institutions, and walk-in clinics. Rates of HIV testing were high, but MSWs reported low access to other STI testing, low insurance coverage, and unmet healthcare needs including primary care, substance use treatment, and mental health services. MSM not engaging in sex work were more likely to report access to primary and specialist care. Rates of HIV testing among these MSM were slightly lower, but they reported more STI testing, more insurance coverage, and fewer unmet needs. Preferred PrEP providers for both groups included primary care physicians, infectious disease specialists, and psychiatrists. MSWs were also willing to access PrEP in substance use treatment and ER settings.

Conclusions

PrEP outreach efforts for MSWs and other MSM should engage diverse providers in many settings, including mental health and substance use treatment, ERs, needle exchanges, correctional institutions, and HIV testing centers. Access to PrEP will require financial assistance, but can build on existing healthcare contacts for both populations.     

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.     

Ambiguity,Ambivalence, and Apprehensions of Taking HIV-1 Pre-Exposure Prophylaxis among Male Couples in San Francisco: A Mixed Methods Study

Objective

We conducted a mixed-methods study to examine serodiscordant and seroconcordant (HIV-positive/HIV-positive) male couples'' PrEP awareness, concerns regarding health care providers offering PrEP to the community, and correlates of PrEP uptake by the HIV-negative member of the couple.

Design

Qualitative sub-study included one-on-one interviews to gain a deeper understanding of participants'' awareness of and experiences with PrEP and concerns regarding health care providers offering PrEP to men who have sex with men (MSM). Quantitative analyses consisted of a cross-sectional study in which participants were asked about the likelihood of PrEP uptake by the HIV-negative member of the couple and level of agreement with health care providers offering PrEP to anyone requesting it.

Methods

We used multivariable regression to examine associations between PrEP questions and covariates of interest and employed an inductive approach to identify key qualitative themes.

Results

Among 328 men (164 couples), 62% had heard about PrEP, but approximately one-quarter were mistaking it with post-exposure prophylaxis. The majority of participants had low endorsement of PrEP uptake and 40% were uncertain if health care providers should offer PrEP to anyone requesting it. Qualitative interviews with 32 men suggest that this uncertainty likely stems from concerns regarding increased risk compensation. Likelihood of future PrEP uptake by the HIV-negative member of the couple was positively associated with unprotected insertive anal intercourse but negatively correlated with unprotected receptive anal intercourse.

Conclusions

Findings suggest that those at greatest risk may not be receptive of PrEP. Those who engage in moderate risk express more interest in PrEP; however, many voice concerns of increased risk behavior in tandem with PrEP use. Results indicate a need for further education of MSM communities and the need to determine appropriate populations in which PrEP can have the highest impact.     

Knowledge of HIV Serodiscordance,Transmission, and Prevention among Couples in Durban,South Africa

Objective

Couples’ voluntary HIV counseling and testing (CVCT) significantly decreases HIV transmission within couples, the largest risk group in sub-Saharan Africa, but it is not currently offered in most HIV testing facilities. To roll out such an intervention, understanding locale-specific knowledge barriers is critical. In this study, we measured knowledge of HIV serodiscordance, transmission, and prevention before and after receipt of CVCT services in Durban.

Design

Pre- and post-CVCT knowledge surveys were administered to a selection of individuals seeking CVCT services.

Methods

Changes in knowledge scores were assessed with McNemar Chi-square tests for balanced data and generalized estimating equation methods for unbalanced data.

Results

The survey included 317 heterosexual black couples (634 individuals) who were primarily Zulu (87%), unemployed (47%), and had at least a secondary level education (78%). 28% of couples proved to be discordant. Only 30% of individuals thought serodiscordance between couples was possible pre‐CVCT compared to 95% post-CVCT. One-third thought there was at least one benefit of CVCT pre‐CVCT, increasing to 96% post‐CVCT. Overall, there were positive changes in knowledge about HIV transmission and prevention. However, many respondents thought all HIV positive mothers give birth to babies with AIDS (64% pre-CVCT, 59% post-CVCT) and that male circumcision does not protect negative men against HIV (70% pre-CVCT, 67% post-CVCT).

Conclusions

CVCT was well received and was followed by improvements in understanding of discordance, the benefits of joint testing, and HIV transmission. Country-level health messaging would benefit from targeting gaps in knowledge about serodiscordance, vertical transmission, and male circumcision.     

Effect of Couples Counselling on Reported HIV Risk Behaviour among HIV Serodiscordant Couples by ART Use,HIV Status and Gender in Rural Uganda

Background

We examined several measures of self-reported HIV risk behaviour in mutually disclosed sero-discordant couples over time to see if a couples counselling intervention was associated with changes in these behaviors.

Methods

We analysed data from a prospective cohort study of HIV sero-discordant couples in Jinja, Uganda collected between June 2009 and December 2011. Participants received couples counselling, at 3-monthly intervals. We examined trends in reported condom-use, number of concurrent sexual partners, knowledge of HIV serostatus of concurrent partners and condom use of concurrent partners using Generalized Estimating Equation models, comparing responses at study enrollment with responses at six, 12 18 and 24 months of follow-up.

Results

A total of 586 couples were enrolled and the female member was HIV positive in 255 (44%) of them. The median age for female participants was 35 years and 42 years for men. Reported condom use at last sex with spouse increased over time (p<0.001) with the largest increases found among couples where the positive participant never received ART during the study(an increase from 68.8% at enrollment to 97.1% at 24 months). Male participants reported reductions in the number of concurrent sexual partners (p<0.001), increase in the knowledge of the HIV serostatus of these partners (p = 0.001) and a trend towards improved condom-use among non-primary partners (p = 0.070). Reported reduced risky behaviors did not wane over the study period.

Conclusion

Couples counselling resulted in increased condom use among all participants and among men the intervention resulted in reductions in risk behaviour with concurrent sexual partners. Routine counselling for serodiscordant couples should be integrated in routine ART care programs.     

HIV Pre-Exposure Prophylaxis Interest among Female Sex Workers in Guangxi,China

Objectives

Acceptability of pre-exposure prophylaxis (PrEP) and willingness to participate in a clinical trial for both safety and efficacy of PrEP were investigated among female sex workers (FSWs) in Guangxi, China.

Methods

A cross-sectional study was performed in three cities in Guangxi. Structured, self-administered questionnaires were used to assess the acceptability of PrEP and the willingness to participate in a clinical trial. Multivariable logistic regression models were fitted to identify predictors.

Results

Among 405 participants, 15.1% had heard of PrEP. If PrEP was deemed to be effective, safe and provided for free, 85.9% reported that they would accept it, and 54.3% of those who accepted PrEP said that they would participate in a clinical trial. The increased acceptability of PrEP was associated with working in male dominated venues, higher income, a poor family relationship, better HIV/AIDS knowledge, not realizing HIV risk from unfamiliar clients, not being forced to use condoms by the gatekeepers, consistent use of condoms, and use of drugs to prevent STD infection. The increased willingness to participate in a clinical trial was associated with a poor family relationship, better HIV/AIDS knowledge, not realizing HIV risk from unfamiliar clients, a willingness to adhere to daily PreP use, and not being concerned about discrimination by others. The main reason for rejecting PrEP or participating in a clinical trial was the concern about the side effects of PrEP.

Conclusions

Acceptability of PrEP among Guangxi FSWs is relatively high, indicating that PrEP intervention programs may be feasible for Chinese FSWs. Given the fact that most of the participants had never heard of PrEP before, and that family, gatekeepers, and social discrimination could significantly affect its acceptability, a comprehensive mix of multiple interventions is necessary for the successful implementation of a PrEP program among this population in Guangxi.     

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 Cost and Impact of Scaling Up Pre-exposure Prophylaxis for HIV Prevention: A Systematic Review of Cost-Effectiveness Modelling Studies

Background

Cost-effectiveness studies inform resource allocation, strategy, and policy development. However, due to their complexity, dependence on assumptions made, and inherent uncertainty, synthesising, and generalising the results can be difficult. We assess cost-effectiveness models evaluating expected health gains and costs of HIV pre-exposure prophylaxis (PrEP) interventions.

Methods and Findings

We conducted a systematic review comparing epidemiological and economic assumptions of cost-effectiveness studies using various modelling approaches. The following databases were searched (until January 2013): PubMed/Medline, ISI Web of Knowledge, Centre for Reviews and Dissemination databases, EconLIT, and region-specific databases. We included modelling studies reporting both cost and expected impact of a PrEP roll-out. We explored five issues: prioritisation strategies, adherence, behaviour change, toxicity, and resistance. Of 961 studies retrieved, 13 were included. Studies modelled populations (heterosexual couples, men who have sex with men, people who inject drugs) in generalised and concentrated epidemics from Southern Africa (including South Africa), Ukraine, USA, and Peru. PrEP was found to have the potential to be a cost-effective addition to HIV prevention programmes in specific settings. The extent of the impact of PrEP depended upon assumptions made concerning cost, epidemic context, programme coverage, prioritisation strategies, and individual-level adherence. Delivery of PrEP to key populations at highest risk of HIV exposure appears the most cost-effective strategy. Limitations of this review include the partial geographical coverage, our inability to perform a meta-analysis, and the paucity of information available exploring trade-offs between early treatment and PrEP.

Conclusions

Our review identifies the main considerations to address in assessing cost-effectiveness analyses of a PrEP intervention—cost, epidemic context, individual adherence level, PrEP programme coverage, and prioritisation strategy. Cost-effectiveness studies indicating where resources can be applied for greatest impact are essential to guide resource allocation decisions; however, the results of such analyses must be considered within the context of the underlying assumptions made. Please see later in the article for the Editors'' Summary     

Efficient Identification of HIV Serodiscordant Couples by Existing HIV Testing Programs in South Brazil

Objective

To examine the feasibility of identifying HIV negative at risk individuals in HIV serodiscordant couples, during voluntary HIV testing in South Brazil.

Methods

We surveyed HIV testers at 4 public testing sites in Rio Grande do Sul. We obtained information on risk behaviors and sexual partnerships. HIV testing and testing for recent infection were performed; HIV prevalence and risk behaviors were assessed among subjects who reported having a steady partner who was HIV positive (serodiscordant group) and compared with the general testing population.

Results

Among 3100 patients, 490 (15.8%) reported being in a steady relationship with an HIV positive partner. New HIV infections were diagnosed in 23% of the serodiscordant group (vs. 13% in the general population, p = 0.01); among newly positive subjects, recent HIV infections were more frequent (23/86, 26.7%) among testers with positive partners than among the general testing group (52/334; 15.6%; p = 0.016). Less than half of the serodiscordant testers reported having used a condom during the last sexual intercourse with their HIV-positive partner. Participants with inconsistent condom use with steady partner were four times more likely to test positive for HIV compared to those who reported always using condoms with the steady partner (OR: 4.2; 95% CI: 2.3 to 7.5).

Conclusion

It is highly feasible to identify large numbers of HIV susceptible individuals who are in HIV serodiscordant relationships in South Brazil testing sites. Condom use within HIV serodiscordant couples is low in this setting, suggesting urgent need for biomedical prevention strategies to reduce HIV transmission.     

A qualitative study of provider thoughts on implementing pre-exposure prophylaxis (PrEP) in clinical settings to prevent HIV infection

Background

A recent clinical trial demonstrated that a daily dose tenofovir disoproxil fumarate and emtricitabrine (TDF-FTC) can reduce HIV acquisition among men who have sex with men (MSM) and transgender (TG) women by 44%, and up to 90% if taken daily. We explored how medical and service providers understand research results and plan to develop clinical protocols to prescribe, support and monitor adherence for patients on PrEP in the United States.

Methods

Using referrals from our community collaborators and snowball sampling, we recruited 22 healthcare providers in San Francisco, Oakland, and Los Angeles for in-depth interviews from May-December 2011. The providers included primary care physicians seeing high numbers of MSM and TG women, HIV specialists, community health clinic providers, and public health officials. We analyzed interviews thematically to produce recommendations for setting policy around implementing PrEP. Interview topics included: assessing clinician impressions of PrEP and CDC guidance, considerations of cost, office capacity, dosing schedules, and following patients over time.

Results

Little or no demand for PrEP from patients was reported at the time of the interviews. Providers did not agree on the most appropriate patients for PrEP and believed that current models of care, which do not involve routine frequent office visits, were not well suited for prescribing PrEP. Providers detailed the need to build capacity and were concerned about monitoring side effects and adherence. PrEP was seen as potentially having impact on the epidemic but providers also noted that community education campaigns needed to be tailored to effectively reach specific vulnerable populations.

Conclusions

While PrEP may be a novel and clinically compelling prevention intervention for MSM and TG women, it raises a number of important implementation challenges that would need to be addressed. Nonetheless, most providers expressed optimism that they eventually could prescribe and monitor PrEP in their practice.     

Incidence of HIV and Syphilis among Men Who Have Sex with Men (MSM) in Beijing: An Open Cohort Study

Background

This study investigated HIV and syphilis incidence among men who have sex with men (MSM) in Beijing, China.

Methods

An open cohort was established from September 2009 to April 2012. Participants were followed up with every three to four months after recruitment and for thirty-one months in total. Chi-square tests were used to compare demographic and behavioral characteristics between participants who were followed up with and those lost to follow up. Univariate and multivariate Cox proportional hazards regression analyses were used to examine demographic and behavioral associations with HIV and syphilis incidence.

Results

69.7% (699/1,003) of the participants finished at least two follow-up surveys during the study period. Variables which corresponded to increased loss to follow-up included younger age, less education, non-identification of homosexual identity, and migrant status. A total of 1,045 person-years (PYs) and 1,016.4 PYs were followed up for HIV and syphilis incidence estimation, respectively. The HIV incidence was 5.9 per 100 PYs and 7.8 per 100 PYs for syphilis. The predictors for the high HIV incidence included unsafe anal sex, sex after drinking alcohol and STI infection.

Conclusion

HIV incidence increased rapidly within the cohort, but syphilis incidence remained stable and decreased. More research is needed to provide multi-pronged HIV prevention interventions among MSM in order to reduce the increasing burden of HIV and sexually transmitted infections (STIs) in China.