Antiretroviral Prophylaxis for HIV Prevention in Heterosexual Men and Women

Department of Global Health, University of Washington, Seattle, WA 98104, USA.
New England Journal of Medicine (Impact Factor: 55.87). 07/2012; 367(5):399-410. DOI: 10.1056/NEJMoa1108524
Source: PubMed


Antiretroviral preexposure prophylaxis is a promising approach for preventing human immunodeficiency virus type 1 (HIV-1) infection in heterosexual populations.
We conducted a randomized trial of oral antiretroviral therapy for use as preexposure prophylaxis among HIV-1-serodiscordant heterosexual couples from Kenya and Uganda. The HIV-1-seronegative partner in each couple was randomly assigned to one of three study regimens--once-daily tenofovir (TDF), combination tenofovir-emtricitabine (TDF-FTC), or matching placebo--and followed monthly for up to 36 months. At enrollment, the HIV-1-seropositive partners were not eligible for antiretroviral therapy, according to national guidelines. All couples received standard HIV-1 treatment and prevention services.
We enrolled 4758 couples, of whom 4747 were followed: 1584 randomly assigned to TDF, 1579 to TDF-FTC, and 1584 to placebo. For 62% of the couples followed, the HIV-1-seronegative partner was male. Among HIV-1-seropositive participants, the median CD4 count was 495 cells per cubic millimeter (interquartile range, 375 to 662). A total of 82 HIV-1 infections occurred in seronegative participants during the study, 17 in the TDF group (incidence, 0.65 per 100 person-years), 13 in the TDF-FTC group (incidence, 0.50 per 100 person-years), and 52 in the placebo group (incidence, 1.99 per 100 person-years), indicating a relative reduction of 67% in the incidence of HIV-1 with TDF (95% confidence interval [CI], 44 to 81; P<0.001) and of 75% with TDF-FTC (95% CI, 55 to 87; P<0.001). Protective effects of TDF-FTC and TDF alone against HIV-1 were not significantly different (P=0.23), and both study medications significantly reduced the HIV-1 incidence among both men and women. The rate of serious adverse events was similar across the study groups. Eight participants receiving active treatment were found to have been infected with HIV-1 at baseline, and among these eight, antiretroviral resistance developed in two during the study.
Oral TDF and TDF-FTC both protect against HIV-1 infection in heterosexual men and women. (Funded by the Bill and Melinda Gates Foundation; Partners PrEP number, NCT00557245.).

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Available from: Wendy Susan Stevens, May 13, 2015
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    • "With several ground-breaking possibilities for women-initiated methods of HIV prevention on the horizon, it is critical to begin planning for product introduction. Recent trials of antiretroviral (ARV)-based prevention products have demonstrated that pre-exposure prophylaxis (PrEP) will be effective if adherence is sufficient [1–5]. Though a lack of efficacy was observed in the FEM-PrEP [6] and VOICE (7) trials of PrEP among young women in sub-Saharan Africa, product use was low as measured by drug levels. "
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    ABSTRACT: Introduction: In planning for the introduction of vaginal microbicides and other new antiretroviral (ARV)-based prevention products for women, an in-depth understanding of potential end-users will be critically important to inform strategies to optimize uptake and long-term adherence. User-centred private sector companies have contributed to the successful launch of many different types of products, employing methods drawn from behavioural and social sciences to shape product designs, marketing messages and communication channels. Examples of how the private sector has adapted and applied these techniques to make decisions around product messaging and targeting may be instructive for adaptation to microbicide introduction. Discussion: In preparing to introduce a product, user-centred private sector companies employ diverse methods to understand the target population and their lifestyles, values and motivations. ReD Associates' observational research on user behaviours in the packaged food and diabetes fields illustrates how 'tag along' or 'shadowing' techniques can identify sources of non-adherence. Another open-ended method is self-documentation, and IDEO's mammography research utilized this to uncover user motivations that extended beyond health. Mapping the user journey is a quantitative approach for outlining critical decision-making stages, and Monitor Inclusive Markets applied this framework to identify toilet design opportunities for the rural poor. Through an iterative process, these various techniques can generate hypotheses on user drop-off points, quantify where drop-off is highest and prioritize areas of further research to uncover usage barriers. Although research constraints exist, these types of user-centred techniques have helped create effective messaging, product positioning and packaging of health products as well as family planning information. These methods can be applied to microbicide acceptability testing outside of clinical trials to design microbicide marketing that enhances product usage. Conclusions: The introduction of microbicide products presents an ideal opportunity to draw on the insights from user-centred private sector companies' approaches, which can complement other methods that have been more commonly utilized in microbicide research to date. As microbicides move from clinical trials to real-world implementation, there will be more opportunities to combine a variety of approaches to understand end-users, which can lead to a more effective product launch and ultimately greater impact on preventing HIV infections.
    Journal of the International AIDS Society 09/2014; 17(3 Suppl 2):19162. DOI:10.7448/IAS.17.3.19162 · 5.09 Impact Factor
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    • "In 2010, the iPrEx study showed that daily oral tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) reduced the risk of HIV infection by 44% among men and transgender women who have sex with men [19]. Additional studies published in 2012 showed that TDF alone or TDF/FTC was also effective in reducing HIV infection in heterosexual men and women in known serodiscordant couples, injecting drug users and other high HIV risk men and women [20–22]. The combination TDF/FTC was approved for use in HIV prevention by the US Food and Drug Administration and WHO released programme guidance in July 2012 with a provisional recommendation on use within the context of demonstration projects for serodiscordant couples, and men and transgender women who have sex with men [23]. "
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    ABSTRACT: Introduction Two new microbicide products based on topical (vaginal) application of antiretroviral drugs – 1% tenofovir gel and the dapivirine ring – are currently in late-stage clinical testing, and results on their safety and effectiveness are expected to become available in early 2015. WHO guidelines on the use of topical pre-exposure prophylaxis (topical PrEP) are important in order to ensure that these new prevention products are optimally used. Discussion Given that these new topical PrEP products are designed to be woman initiated and will likely be delivered in reproductive health settings, it is important to ensure that the guidance be framed in the context of comprehensive sexual and reproductive health and human rights. In addition to the safety and effectiveness data resulting from clinical trials, and the regulatory approval required for new products, the WHO normative guidelines on the use of topical PrEP will be essential for rapid roll-out in countries. Conclusions Human rights standards and principles provide a framework for the provision of woman-initiated HIV prevention products. These include addressing issues related to the gender inequities which are linked to the provision of HIV-prevention, treatment and care for young girls and women. Effective programming for women and girls must therefore be based on understanding the local, social and community contexts of the AIDS epidemic in the country, and adapting HIV strategies and programmes accordingly. Such a framework therefore is needed not only to ensure optimal uptake of these new products by women and girls but also to address sociocultural barriers to women's and girls’ access to these products.
    Journal of the International AIDS Society 09/2014; 17(3 Suppl 2):19279. DOI:10.7448/IAS.17.3.19279 · 5.09 Impact Factor
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    • "In July 2010, the CAPRISA 004 clinical trial of tenofovir 1% gel demonstrated that an ARV-based vaginal gel could prevent acquisition of HIV [1]. Subsequently, results from the iPrEX, Partners PrEP, TDF2 and Bangkok Tenofovir trials of oral ARV dosing further bolstered confidence in ARV-based prevention [2–5]. In each of these trials, sub-analyses indicated that poor adherence to the prescribed dosing regimen reduced efficacy. "
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    ABSTRACT: Introduction Product adherence and its measurement have emerged as a critical challenge in the evaluation of new HIV prevention technologies. Long-acting ARV-based vaginal rings may simplify use instructions and require less user behaviour, thereby facilitating adherence. One ARV-based ring is in efficacy trials and others, including multipurpose rings, are in the pipeline. Participant motivations, counselling support and measurement challenges during ring trials must still be addressed. In previous HIV prevention trials, this has been done largely using descriptive and post-hoc methods that are highly variable and minimally evaluated. We outline an interdisciplinary framework for systematically investigating promising strategies to support product uptake and adherence, and to measure adherence in the context of randomized, blinded clinical trials. Discussion The interdisciplinary framework highlights the dual use of adherence measurement (i.e. to provide feedback during trial implementation and to inform interpretation of trial findings) and underscores the complex pathways that connect measurement, adherence support and enacted adherence behaviour. Three inter-related approaches are highlighted: 1) adherence support – sequential efforts to define motivators of study product adherence and to develop, test, refine and evaluate adherence support messages; 2) self-reported psychometric measures – creation of valid and generalizable measures based in easily administered scales that capture vaginal ring use with improved predictive ability at screening, baseline and follow-up that better engage participants in reporting adherence; and 3) more objective measurement of adherence – real-time adherence monitoring and cumulative measurement to correlate adherence with overall product effectiveness through innovative designs, models and prototypes using electronic and biometric technologies to detect ring insertion and/or removal or expulsion. Coordinating research along these three pathways will result in a comprehensive approach to product adherence within clinical trials. Conclusions Better measurement of adherence will not, by itself, ensure that future effectiveness trials will be able to address the most basic question: if the product is used per instructions, will it prevent HIV transmission? The challenges to adherence measurement must be addressed as one component of a more integrated system that has as its central focus adherence as a behaviour emerging from the social context of the user.
    Journal of the International AIDS Society 09/2014; 17(3 Suppl 2):19158. DOI:10.7448/IAS.17.3.19158 · 5.09 Impact Factor
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