Biomedical HIV Prevention Strategies Research Articles

Unpacking the Influence of Sexual Stigma on HIV Risk: Results From a Prospective Study of Men Who Have Sex With Men in Beijing, China.

We examined the mediating roles of coping, depression, anxiety, and encountering difficult sexual situations in explaining the association between stigma against men who have sex with men (MSM) and HIV risk. We conducted path analyses using longitudinal data collected from 493 Chinese MSM in Beijing at baseline, 6 months, and 12 months from 2011 to 2013. MSM stigma, specifically anticipations of stigma, had a marginally significant, protective total effect on unprotected anal intercourse at 12 months. This overall association, however, was the byproduct of 5 significant, indirect associations (3 risk enhancing, 2 protective) that routed through coping, anxiety, and difficult sexual situations. Of note, heavier use of avoidant coping principally had a protective effect on risk behavior by decreasing difficult sexual situations. Interventions to reduce avoidant coping would be an important tool for improving the emotional well-being of Chinese MSM. Such interventions, however, must be paired with biomedical or behavioral HIV prevention strategies to ensure that their benefit is not undermined by unintended increased HIV transmission risk in response to reduced social isolation among MSM.

“I never thought that it would happen … ” Experiences of HIV seroconverters among HIV-discordant partnerships in a prospective HIV prevention study in Kenya

ABSTRACTIn spite of access to behavioral and biomedical HIV prevention strategies, HIV transmission occurs. For HIV-serodiscordant couples, prevention programs can be tailored to address individual and couples’ needs to preserve their relationship while minimizing HIV risk. Programs for serodiscordant couples may benefit from learning from experiences of couples who transmit HIV. We conducted 20 individual in-depth interviews with 10 initially HIV-serodiscordant couples who transmitted HIV during prospective follow-up at a peri-urban research site in Thika, Kenya. Data were analyzed inductively to identify situations that led to prevention failure and coping mechanisms. Inconsistent condom use driven by low HIV risk perception and alcohol use often preceded seroconversion while persistent blame frequently hindered couples’ communication soon after seroconversion. In this emerging era of antiretroviral-based HIV prevention, couples’ counseling can capitalize on opportunities to foster a supportive environment to discuss initiation and adherence to time-limited pre-exposure prophylaxis and lifelong antiretroviral therapy, in addition to strategies to reduce alcohol use, diffuse blame, and use condoms.

Optimizing Delivery of Preexposure Prophylaxis--The Next Frontier.

Preexposure prophylaxis (PrEP) for human immunodeficiencyvirus(HIV) infection—administeringadailytabletofaUSFood and Drug Administration (FDA)-approved HIV antiretroviral fixed-dose combination of tenofovirdisoproxil fumarate and emtricitabine (TDF/FTC) (Truvada; Gilead Sciences, Inc) to high-risk uninfected individuals—has galvanized supporters and opponents. Data show that PrEP is effective in preventing HIV infections inmenwho have sexwithmen (MSM), aswell as in heterosexually active men and women.1-3 In intention-to-treat analyses, these studies showed reductions of infections between44%and 75%, although compliancewith daily therapy did not appear to be high. When investigators restricted the analysis to personswith detectable drug levels, effectiveness rates were over 90%. An open label extension study in follow-up to the iPrEX (Iniciativa Profilaxis Pre-Exposicion) trial1 found 100% protection for those who had sustained adherence at the level of 4 or more doses per week.4 Whether adherence to daily or near-daily dosing can be achieved in real-world settings has been questioned. Moreover, there has been concern that PrEP will lead to increases in condomless sexwith attendant risk of other sexually transmitted infections. In this issueofJAMAInternalMedicine, Liuandcolleagues5 address some of these concerns as they report the results of theDemoProject, a longitudinal, open-label, single-armstudy ofdailyoralTDF/FTC inmenwhohavesexwithmenandtransgenderwomen in3cities.This report represents the firstof several demonstration projects following the 2012 FDA approval of TDF/FTC for HIV prevention. Deployed at clinics that treat sexually transmitted infections (STIs) in San Francisco and Miami, aswell as a gay-identified community health center in Washington,DC, thestudyenrolled550menwhohavesexwith menand7 transgenderwomen intoa48-week longitudinal cohort between October 2012 and February 2014. Importantly, this is the first cohort studied that received open-label TDF/ FTCwhohadnotpreviouslyparticipated in a randomized trial of PrEP, therefore, providing a better approximation of what real-world clinical PrEP delivery might look like. Overall, thenews concerningPrEPdissemination is good, but there are sobering lessons.Of the557enrolled in theDemo study,5 78% were retained over the 48 weeks of follow-up. African Americans and participants from theMiami sitewere less likely to be retained, as were those with lower socioeconomic status and the uninsured. In an attempt tomimic clinical settings,missing participantswere only contacted amaximum of 3 times in response to a missed visit, and incentives for visit attendancewerenominal, although thedrugwas free. The study used intraerythrocytic drug levels measured on dried blood spots (DBS).5 This is an elegant technology for evaluating TDF-based adherence over a 3to 4-month horizon.6 Such a measurement provides an objective biomarker for longitudinal adherence. A subset of approximately 100 participants at each site had DBS drug level assays performed. At any given time over the 48-week follow-up period, 80% to 86% of study participants had DBS levels commensurate with high levels of protection (≥4 doses per week or the adherence modeled to be predictive of 96% protection based on the iPrEX data set7 and 100% protective from iPrEX open label extension). Reassuringly, those reporting higher sexual risk were more likely to have protective biomarker levels, but consistently, the black participants and those fromMiami were less likely to have protective levels, as were participants who were unstably housed. The overall HIV incidence in the cohortwas an extremely low 0.43 per 100 person years (95% CI, 0.05-1.54). Of 2 onstudy seroconversions observed, both occurred in participants whose DBS suggested PrEP adherence levels of fewer than 2 doses per week. In the Demo study,5 the observation of poor retention and adherence inMiamiarenotexplainedbydemographicsorother measured parameters, which reminds us that community and individual acceptance of PrEP may still vary widely by region andculture, andwide-reachingandnovel educationalmessagingwill need tobeused to assure coverageof all at-risk groups. Overall, the rates of unprotected intercourse and STIs in the Demo study5 were high but stable over the course of the study. It remains unclear if the high rates of STIs are a manifestation of testing bias or a suggestion of increased rates of condomless sex. The medications were well tolerated with minimal adverse effects. The sites in theDemostudy5 are sophisticated,highlymotivated sites that arewell-versed in PrEP science, well-rooted in community activities, andexperiencedwithbehavioral and biomedicalHIVprevention strategies. Their successes inPrEP delivery may not be generalizable to other clinical settings. There are an abundance of anecdotes on the Internet of potential PrEP consumers struggling to find clinics willing to provide PrEP and knowledgeable about monitoring and concomitant services. PrEP-providing clinic registries are being developed but are largely grassroots efforts. Financial coverage of copayments and deductibles can be a substantial barrier, and self-efficacy (ie, high levels of motivation, empowerment, knowledge, and time) seems tobe anecessaryquality for patients and clinics alike to marshal the available financial resources. Whether the retention and adherence rates found in this studyaregeneralizable to lesswell-resourcedand sophisticated clinical settings remains to be seen. Related articles pages 75 and 136 Preexposure Prophylaxis for HIV Infection Original Investigation Research

What is the benefit of the biomedical and behavioral interventions in preventing HIV transmission?

Scientific evidence supports the synergy between biomedical and behavioral interventions aimed at preventing the transmission of HIV as a strategy to eradicate AIDS. To characterize comparatively the benefits from biomedical and behavioral interventions to prevent HIV transmission. Narrative review. We performed a comparative analysis of the benefits of studied interventions by means of estimating the number needed to treat (NNT). Evaluated interventions: counseling activities for behavior change to prevent exposure to HIV; antiretroviral pre-exposure prophylaxis (PrEP) and antiretroviral post-exposure prophylasis (PEP) for HIV and treatment of serodiscordant couples as a strategy for prevention of HIV transmission (TasP). counseling interventions and TasP have smaller NNTs, equal to, respectively, 11 (95%CI 9 - 18) at 12 months and 34 (95%CI 23 - 54) in 42 months comparatively to PrEP interventions, that resulted in 41 (95%CI 28 - 67) individuals receiving antiretrovirals in order to prevent one case of HIV infection at 36 months for men and serodiscordant couples. PEP interventions are associated with protective effects estimated at 81%. Lack of trials evaluating PEP prevents estimate of NNT. The estimate of the NNT can be a helpful parameter in the comparison between the effectiveness of different behavioral and biomedical HIV prevention strategies. Studies evaluating the benefit and safety of combined behavioral and biomedical interventions are needed, especially considering the attributable fraction of each component. Integration of behavioral and biomedical interventions is required to achieve complete suppression of the virus, and thus reducing viral replication, infectivity and the number of cases.

Rethinking HIV prevention to prepare for oral PrEP implementation for young African women.

IntroductionHIV incidence remains high among young women in sub-Saharan Africa in spite of scale-up of HIV testing, behavioural interventions, antiretroviral treatment and medical male circumcision. There is a critical need to critique past approaches and learn about the most effective implementation of evidence-based HIV prevention strategies, particularly emerging interventions such as pre-exposure prophylaxis (PrEP).DiscussionWomen in sub-Saharan Africa are at increased risk of HIV during adolescence and into their 20s, in part due to contextual factors including gender norms and relationship dynamics, and limited access to reproductive and sexual health services. We reviewed behavioural, behavioural economic and biomedical approaches to HIV prevention for young African women, with a particular focus on the barriers, opportunities and implications for implementing PrEP in this group. Behavioural interventions have had limited impact in part due to not effectively addressing the context, broader sexual norms and expectations, and structural factors that increase risk and vulnerability. Of biomedical HIV prevention strategies that have been tested, daily oral PrEP has the greatest evidence for protection, although adherence was low in two placebo-controlled trials in young African women. Given high efficacy and effectiveness in other populations, demonstration projects of open-label PrEP in young African women are needed to determine the most effective delivery models and whether women at substantial risk are motivated and able to use oral PrEP with sufficient adherence to achieve HIV prevention benefits.ConclusionsSocial marketing, adherence support and behavioural economic interventions should be evaluated as part of PrEP demonstration projects among young African women in terms of their effectiveness in increasing demand and optimizing uptake and effective use of PrEP. Lessons learned through evaluations of implementation strategies for delivering oral PrEP, a first-generation biomedical HIV prevention product, will inform development of new and less user-dependent PrEP formulations and delivery of an expanding choice of prevention options in HIV prevention programmes for young African women.

Getting PrEPared for HIV Prevention Navigation: Young Black Gay Men Talk About HIV Prevention in the Biomedical Era

Biomedical HIV prevention strategies, such as pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP), represent new opportunities to reduce critically high HIV infection rates among young black men who have sex with men (YBMSM). We report results of 24 dyadic qualitative interviews (N=48), conducted in Los Angeles, CA, exploring how YBMSM and their friends view PrEP and PEP. Interviews were analyzed using a grounded theory approach. Participants had widely divergent levels of knowledge about these prevention methods. Misconceptions and mistrust regarding PrEP were common, and concerns were expressed about PrEP-related stigma and the potential for gossip among peers who might assume a person on PrEP was HIV-positive. Yet participants also framed PrEP and PEP as valuable new options within an expanded "tool kit" of HIV prevention strategies that created possibilities for preventing new HIV infections, dating men with a different HIV status, and decreased anxiety about exposure to HIV. We organized themes around four main areas: (1) information and misinformation about biomedical HIV prevention; (2) expectations about PrEP, sexual behavior, and stigma; (3) gossip, disclosure, and "spreading the word" about PrEP and PEP; and (4) the roles of PrEP and PEP in an expanded HIV prevention tool kit. The findings suggest a need for guidance in navigating the increasingly complex array of HIV-prevention options available to YBMSM. Such "prevention navigation" could counter misconceptions and address barriers, such as stigma and mistrust, while helping YBMSM make informed selections from among expanded HIV prevention options.

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.

BackgroundRapid 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.MethodsWe 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.ResultsA 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.ConclusionsWhen 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.

The Road Ahead: Working Towards Effective Clinical Translation of Biomedical HIV Prevention Strategies

ABSTRACT Emerging evidence from several randomized controlled trials show that antiretroviral-based biomedical HIV prevention interventions are efficacious in preventing HIV if they are taken as directed, and could potentially reduce the number of new HIV infections globally. Strategies such as treatment as prevention and use of oral pre-exposure prophylaxis for HIV prevention have shown great promise, yet have raised important implementation concerns around awareness and acceptance, delivery, adherence, side effects, risk compensation, cost–effectiveness and drug resistance. In order to address these issues, a number of treatment as prevention and pre-exposure prophylaxis demonstration projects have been initiated to assess the feasibility of introducing these interventions in ‘real-world’ settings. These projects will be instrumental in determining best practices for optimal delivery and sustainability of these HIV prevention interventions. The road to effective translation to clinical setting is promising, but comes with challenges which are not insurmountable.

Comparing male escorts' sexual behaviour with their last male client versus non-commercial male partner

Apart from research suggesting that male escorts are less likely to have condomless anal sex (CAS) with their male clients compared with male non-clients, little is known about how male escorts' behaviour differs between their clients and non-clients. In spring 2013, 387 Internet-based male escorts completed an online survey that included identical questions about their sexual behaviour with their last male client and male non-client. Encounters with non-commercial partners were significantly more likely to involve a greater range of sexual behaviours, including giving oral sex to partner, kissing, anal receptive sex and sex without condoms. These findings suggest that escorts may display a greater sexual repertoire with non-commercial partners compared to their clients. Encounters with non-commercial partners were also rated as more satisfying than with clients. Condomless anal sex was less common with clients, suggesting that escorts and clients may take active roles in mitigating risks for HIV and STI transmission with each other. Although the modal response for CAS was to abstain, more than half of participants reported CAS during at least one of the two encounters assessed. Behavioural and/or biomedical HIV-prevention strategies would be appropriate for some male escorts to reduce HIV transmission risk.

Sexual Partnerships and Considerations for HIV Antiretroviral Pre-Exposure Prophylaxis Utilization Among High-Risk Substance Using Men Who Have Sex with Men

Men who have sex with men (MSM) remain at great risk of HIV in the United States, representing 65% of incident HIV infections. One factor contributing to the high rate of HIV infection among MSM is use of "recreational" drugs that are highly associated with unprotected anal sex. Pre-exposure chemoprophylaxis (PrEP) is a novel biomedical HIV prevention strategy that has the potential to reduce HIV transmission in MSM. Main and casual sex partners play a role in HIV prevention efforts for MSM. The study aimed to qualitatively explore the perceived influences of sexual relationships on promoting and inhibiting PrEP use among high-risk MSM who report regular drug use. Semi-structured qualitative interviews were conducted with 40 participants recruited in Boston, Massachusetts. Data were analyzed using descriptive qualitative analysis. Casual partners presented a distinct set of concerns from primary partnerships. MSM generally viewed main partners as a potential source of support for taking PrEP. Given their informal and often temporary nature, PrEP disclosure to casual partners was considered unnecessary. HIV-related stigma and substance use were also perceived as barriers to discussing PrEP use with casual partners. MSM articulated a high degree of personal agency regarding their ability to take PrEP. Findings suggest that behavioral interventions to improve PrEP utilization and adherence for high-risk MSM should be tailored to sex partner type and the parameters established between sex partners. Approaches to PrEP disclosure and partner engagement should be informed by the relative benefits and limitations characterized by these different types of relationships.

Averting HIV Infections in New York City: A Modeling Approach Estimating the Future Impact of Additional Behavioral and Biomedical HIV Prevention Strategies

BackgroundNew York City (NYC) remains an epicenter of the HIV epidemic in the United States. Given the variety of evidence-based HIV prevention strategies available and the significant resources required to implement each of them, comparative studies are needed to identify how to maximize the number of HIV cases prevented most economically.MethodsA new model of HIV disease transmission was developed integrating information from a previously validated micro-simulation HIV disease progression model. Specification and parameterization of the model and its inputs, including the intervention portfolio, intervention effects and costs were conducted through a collaborative process between the academic modeling team and the NYC Department of Health and Mental Hygiene. The model projects the impact of different prevention strategies, or portfolios of prevention strategies, on the HIV epidemic in NYC.ResultsTen unique interventions were able to provide a prevention benefit at an annual program cost of less than $360,000, the threshold for consideration as a cost-saving intervention (because of offsets by future HIV treatment costs averted). An optimized portfolio of these specific interventions could result in up to a 34% reduction in new HIV infections over the next 20 years. The cost-per-infection averted of the portfolio was estimated to be $106,378; the total cost was in excess of $2 billion (over the 20 year period, or approximately $100 million per year, on average). The cost-savings of prevented infections was estimated at more than $5 billion (or approximately $250 million per year, on average).ConclusionsOptimal implementation of a portfolio of evidence-based interventions can have a substantial, favorable impact on the ongoing HIV epidemic in NYC and provide future cost-saving despite significant initial costs.

From modeling to morals: Imagining the future of HIV PREP in Lesotho

Amidst growing global endorsements of new biomedical HIV prevention strategies, ARV-based pre-exposure prophylaxis (ARV PrEP) has garnered considerable attention as a potentially promising prevention strategy. Though it may offer more effective protection for certain at-risk groups than conventional prevention strategies (such as sexual partner reduction, condom use, and prevention of mother-to-child transmission), PrEP is more costly. PrEP requires more ongoing contact between individuals and providers, and a level of surveillance from the health system that is not necessary with other preventive measures. In this sense, it represents a new bio-technology for HIV prevention that poses particular challenges for worldwide implementation, given developing countries' struggling health systems and incomplete HIV treatment programs. Since the emergence of PrEP has stimulated ethical discussions premised on incomplete knowledge of efficacy and implementation, this paper explores the ethical parameters of a likely scenario for PrEP usage in a single, resource-poor country. We first develop a plausible model for PrEP deployment and utilization based on current PrEP research, while carefully considering the reigning institutional values of feasibility and effectiveness in global health approaches. Drawing on ethnographic research of HIV treatment and prevention approaches in Lesotho, we address ethical questions arising from this scenario of PrEP delivery. Lesotho presents a compelling and emblematic case study of PrEP's potential successes and pitfalls in a developing country, given the country's high HIV prevalence, struggles to achieve universal access to HIV treatment regimes, continued existence of stigma around the epidemic, and difficulties in addressing persistent social inequalities that fuel infections.

A typology of structural approaches to HIV prevention: A commentary on Roberts and Matthews

Renewed enthusiasm for biomedical HIV prevention strategies has followed the recent publication of several high-profile HIV antiretroviral therapy-based HIV prevention trials. In a recent article, Roberts and Matthews (2012) accurately note some of the shortcomings of these individually targeted approaches to HIV prevention and advocate for increased emphasis on structural interventions that have more fundamental effects on the population distribution of HIV. However, they make some implicit assumptions about the extent to which structural interventions are user-independent and more sustainable than biomedical or behavioral interventions. In this article, I elaborate a simple typology of structural interventions along these two axes and suggest that they may be neither user-independent nor sustainable and therefore subject to the same sustainability concerns, costs, and potential unintended consequences as biomedical and behavioral interventions.

S3.5 Scaling up novel biomedical HIV prevention strategies: evidence for action

Randomised controlled trial results can provide the scientific rationale for implementing new biomedical HIV prevention strategies but are not sufficient. Generalisability of trial findings, good participatory trial conduct, acceptability studies,...

The emerging role of antiretroviral agents in HIV prevention

There has been increasing focus on the potential for oral antiretroviral agents (ARV) to prevent sexual transmission of HIV. ARVs can theoretically be used in three ways to prevent sexual transmission of HIV: as pre-exposure prophylaxis (PrEP), as post-exposure prophylaxis (PEP) or by effective treatment of those infected with HIV to reduce infectivity and transmission to sexual partners (‘treatment as prevention’). The administration of PEP after occupational exposure to HIV has been the standard of care in health care settings in Australia since the early 1990s. In December 1998, New South Wales became the first Australian state to introduce guidelines recommending PEP for HIV in the context of non-occupational exposures (NPEP) such as sexual and injecting exposures. In July 2001, the Australian National Council on AIDS, Hepatitis C and Related Diseases released national guidelines recommending NPEP after high-risk exposures and these guidelines were revised in 2007. Worldwide, many countries have now published guidelines regarding the use of NPEP. Most guidelines recommend that NPEP be commenced within 72h of exposure, with the exception of European guidelines, which recommend commencement within 48 h. UK and European guidelines recommend three drug regimens for NPEP, whereas the World Health Organization, Australian and USA guidelines recommend two or three drug regimens, prescribed according to the level of risk from the reported exposure. NPEP is the only biomedical HIV prevention strategy (apart from male condoms) that is widely available and promoted in Australia. NPEP programs that are targeted towards high-risk individuals have been successfully implemented in Australia without evidence of high levels of inappropriate prescription. Although NPEP is likely to have been successful at preventing HIV on an individual level, it has had very limited populationlevel impact in terms of the total number of HIV seroconversions prevented. Global implementation of NPEP has been constrained by limited resources and by the absence of data from randomised controlled trials of NPEP efficacy. The likelihood of such trials occurring is remote, given the ethical difficulties of a placebo controlled arm when PEP has been made widely available for prevention in the occupational setting and for maternal-child transmission. The research from Victoria, Australia, published in this issue of the Journal, reports on a large cohort that comprised nearly all NPEP users in Victoria. The findings of very low rates of potential NPEP failure are consistent with findings from numerous other observational studies of cohorts of NPEP users. Nevertheless, case reports of HIV seroconversions due to NPEP failure have been reported, even after fully adherent NPEP use. In addition, concerns have been raised over the impact of NPEP use on subsequent HIV risk behaviour. Studies examining this issue have concluded that risk behaviour does not increase, particularly when NPEP is combined with behavioural counselling. It has been hypothesised that universal treatment of all HIV-positive individuals within a population may decrease HIV transmission at the population level (‘treatment as prevention’). This prevention-centred approach to ARV treatment is being explored in a randomised controlled trial of early versus standard ARV therapy of HIV-infected individuals in serodiscordant couples. The results of this trial will provide information on the role of HIV treatment in HIV prevention in heterosexuals but no meaningful information for homosexual men. As there are no published studies of HIV viral load and HIV transmission in serodiscordant couples which include homosexual men, we know nearly nothing on HIV treatment as prevention when HIV transmission is occurring through anal intercourse. Studies which quantify the rate of transmission through anal intercourse by HIV viral load are urgently needed. ARV agents may also potentially be useful in reducing HIV transmission risk before a risk event. In the USA, expanded PrEP safety studies for men who have sex with men have just concluded. Recently presented data showed no serious adverse events and no significant effect of PrEP on HIV risk. Several other PrEP trials are due for completion and will be reported in the near future. It is critical that NPEP policymakers and providers alike now consider what the imminent release of the results of randomised trials of PrEP efficacy will mean for NPEP programs and utilisation in Australia. If PrEP is shown to be effective, the role of NPEP as an HIV prevention strategy may be in question. For example, the delineation between PrEP and NPEP will be unclear, particularly for those people who are possibly exposed to HIV more than once a month where the PrEP and NPEP administration periods may overlap. Australian regulatory authorities and policymakers will need to grapple with the issue of who funds a new expensive HIV CSIRO PUBLISHING Editorial