Real World Adherence to HIV PrEP in Serodiscordant African Couples

描述（由申请方提供）：口服暴露前预防（PrEP）预防HIV感染已在男男性行为者、血清不一致夫妇和年轻异性恋者中证明有效;然而，在两项女性研究中未显示有效性。缺乏依从性是这些不一致结果的主要假设。严格的临床试验之外的依从性是未知的，为了确定PrEP是否会成为一种有效的公共卫生策略，必须知道这一点。这项拟议的研究将确定临床试验之外血清不一致夫妇中的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：这项研究建立在我们在合作伙伴PrEP研究（替诺福韦和恩曲他滨/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，并将纳入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提供模式研究，涉及乌干达和肯尼亚的500对血清不一致夫妇（R 01 MH 095507，PI：Baeten）。我们的具体目标如下：1）评估在公共卫生提供模型中接受PrEP的研究初始不一致夫妇中PrEP依从性的水平，轨迹和相关性，其中依从性咨询可用于扩大规模; 2）确定依从性模式与临床试验外风险暴露之间的关系;和3）确定目标1和2中确定的真实的世界依从性和风险暴露的水平和模式是否实质上改变了当前对PrEP有效性和成本效益的估计。创新：我们将：1）描述招募到PrEP交付示范项目中的血清不一致夫妇的PrEP依从性，该项目涉及对规模扩大环境实用的有限依从性咨询; 2） 使用新的概念框架来理解PrEP依从性行为; 3）使用性行为的短信报告结合电子依从性监测来表征性暴露和PrEP依从性的时间模式;和4）开发替诺福韦药物浓度-时间关系模型，使用前瞻性收集的样品，其可用于确定哪种粘附模式可能足以保护免受HIV感染。研究者：Jessica Haberer博士是一位新的研究人员，在撒哈拉以南非洲研究抗逆转录病毒治疗和PrEP的依从性方面具有丰富的经验。她的团队包括临床流行病学（Jared Baeten博士和Connie Celum博士），依从性测量（大卫Bangsberg博士），定性分析（Norma Ware博士），替诺福韦药代动力学建模（克雷格亨德里克斯和Ayyappa Chaturvedula博士），统计分析（Deborah Donnell博士），成本效益建模（Tim Hallett博士）和撒哈拉以南非洲研究经验（Nelly Mugo和Elly Katabira博士）。

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).