Real World Adherence to HIV PrEP in Serodiscordant African Couples

描述（由申请人提供）：口服暴露前预防HIV感染（PrEP）已被证明对男男性行为者、血清不一致的夫妇和年轻异性恋者有效；然而，在两项针对女性的研究中并未显示出疗效。缺乏依从性是这些差异发现的主要假设。严格的临床试验之外的依从性是未知的，为了确定PrEP是否将是一项有效的公共卫生战略，了解这一点至关重要。拟议的研究将确定在临床试验之外血清不一致的夫妇中未感染艾滋病毒的人是否能够充分坚持PrEP以防止艾滋病毒传播。方法：本研究建立在我们在伙伴PrEP研究（替诺福韦和恩曲西他滨/替诺福韦PrEP的III期临床试验）中进行依从性子研究的经验基础上，并将整合到最近资助的一项基于抗逆转录病毒治疗的艾滋病毒预防策略的公共卫生交付模式研究中，该研究涉及乌干达和肯尼亚的500对血清不一致的夫妇（R01MH095507, PI: Baeten）。我们的具体目标如下：1)评估在公共卫生服务模式下接受PrEP的未接受研究的不和谐夫妇的PrEP依从性水平、轨迹和相关因素，并为扩大依从性提供实用的咨询；2)确定依从性模式与临床试验之外的风险暴露之间的关系；3)确定目标1和2中确定的现实世界依从性和风险暴露的水平和模式是否大大改变了目前对PrEP有效性和成本效益的估计。创新：我们将：1)对纳入PrEP提供示范项目的血清不一致夫妇的PrEP依从性进行特征描述，该示范项目包括有限的依从性咨询，可用于扩大规模；2）

DESCRIPTION (provided by applicant): Oral pre-exposure prophylaxis (PrEP) against HIV infection has demonstrated efficacy in men who have sex with men, serodiscordant couples, and young heterosexuals; however, efficacy was not shown in two studies of women. Lack of adherence is the leading hypothesis for these discrepant findings. Adherence outside of rigorous clinical trials is unknown and is essential to know in order to determine whether PrEP will be an effective public health strategy. The proposed study will determine if HIV-uninfected people in serodiscordant couples outside a clinical trial will adhere adequately enough to PrEP to be protected against HIV transmission. Approach: This study builds on our experience conducting the Adherence Sub-study within the Partners PrEP Study (a phase III clinical trial of tenofovir and emtricitabine/tenofovir PrEP) and will be integrated into a recently funded study of a public health delivery model of antiretroviral therapy-based HIV prevention strategies involving 500 serodiscordant couples in Uganda and Kenya (R01MH095507, PI: Baeten). Our Specific Aims are a follows: 1) Assess the level, trajectory, and correlates of PrEP adherence in research-naive discordant couples receiving PrEP in a public health delivery model with adherence counseling practical for scale-up; 2) Determine the relationship between patterns of adherence and risk exposure outside of a clinical trial; and 3) Determine if the level and patterns of real world adherence and risk exposure determined in Aims 1 and 2 substantially alter current estimates of PrEP effectiveness and cost-effectiveness. Innovation: We will: 1) characterize PrEP adherence in serodiscordant couples recruited into a demonstration project of PrEP delivery involving limited adherence counseling that is practical for scale-up settings; 2) use a novel conceptual framework to understand PrEP adherence behavior; 3) use text message reports of sexual behavior combined with electronic adherence monitoring to characterize temporal patterns of sexual exposure and PrEP adherence; and 4) develop models of the tenofovir drug concentration-time relationship, using prospectively collected samples, which can be used to determine which patterns of adherence are likely adequate for protection against HIV infection. Investigators: Dr. Jessica Haberer is a new investigator with significant experience studying adherence to antiretroviral therapy and PrEP in sub-Saharan Africa. Her team includes expertise in clinical epidemiology (Drs. Jared Baeten and Connie Celum), adherence measurement (Dr. David Bangsberg), qualitative analysis (Dr. Norma Ware), tenofovir pharmacokinetic modeling (Drs. Craig Hendrix and Ayyappa Chaturvedula), statistical analysis (Dr. Deborah Donnell), cost-effective modeling (Dr. Tim Hallett), and sub-Saharan African research experience (Drs. Nelly Mugo and Elly Katabira).