Real World Adherence to HIV PrEP in Serodiscordant African Couples

现实世界中血清不一致的非洲夫妇对 HIV PrEP 的遵守情况

• 批准号: 8465580
• 负责人: Jessica Elizabeth Haberer
• 金额: $ 62.66万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-04 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8465580
• 关键词: AIDS prevention; Acute; Address; Adherence; Africa South of the Sahara; African; Behavior; Behavior Therapy; Build-it; Clinical Trials; Consensus; Counseling; Couples; Data; Dose; Effectiveness; Electronics; Emotional Bonds; Epithelium; Event; Fertility; Frequencies; Funding; HIV; HIV Infections; HIV Seropositivity; Health Care Costs; Heterogeneity; Heterosexuals; Individual; Infection; Intervention; Interview; Investigation; Investments; Kenya; Link; Measurement; Measures; Modeling; Monitor; Motivation; Oral; Participant; Pattern; Persons; Pharmaceutical Preparations; Phase III Clinical Trials; Placebos; Prevention strategy; Prophylactic treatment; Protocols documentation; Public Health; Recruitment Activity; Reporting; Research; Research Personnel; Risk; Sampling; Sex Behavior; Surveys; System; Tenofovir; Text; Theoretical model; Time; Trust; Uganda; United States National Institutes of Health; Vagina; Visit; Woman; Work; antiretroviral therapy; base; clinical epidemiology; cost; cost effective; cost effectiveness; design; emtricitabine; experience; high risk; improved; innovation; mathematical model; member; men who have sex with men; novel; open label; pharmacokinetic model; pill; public health relevance; scale up; sexual relationship; transmission process

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).

描述（由申请人提供）：针对HIV感染的口服预防（PREP）对与男性发生性关系的男性，精神错乱的夫妻和年轻异性恋者表现出疗效；但是，两项研究中未显示功效。缺乏依从性是这些差异发现的主要假设。在严格的临床试验之外的依从性是未知的，必须知道要确定PREP是否是有效的公共卫生战略。拟议的研究将确定在临床试验外的血清旁夫妇中，艾滋病毒未感染的人是否会充分粘附以进行准备以防止艾滋病毒传播。方法：这项研究以我们在合作伙伴准备研究中进行依从性子研究的经验为基础（III阶段的Tenofovir和Emtritobine/Tenofovir Prep），并将集成到最近资助的基于抗逆转录病毒治疗的公共卫生交付模型的基于抗逆转录病毒治疗的公共卫生交付模型的研究中Baeten）。我们的具体目的是：1）评估在公共卫生提供模型中接受PREP的研究中的遵守水平，轨迹和相关性，并遵守辅助咨询，以实用扩大规模； 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）确定在目标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实质上改变了当前的预期有效性和成本效益的估计。创新：我们将：1）描述在招募的精华徒夫妻中，被招募到示威的准备项目中，涉及有限的依从性咨询，这对于扩大规模的环境是实际的； 2） 使用一个新颖的概念框架来理解准备依从性行为； 3）使用性行为的文本消息报告与电子依从性监控相结合，以表征性暴露和依从性的时间模式； 4）使用前瞻性收集的样品开发替诺福韦药物浓度时间关系的模型，这些样品可用于确定哪些粘附模式可能足以保护抗HIV感染。研究人员：杰西卡·哈伯勒（Jessica Haberer）博士是一名新的研究者，在撒哈拉以南非洲遵守抗逆转录病毒疗法和PREP方面具有丰富的经验。 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撒哈拉以南非洲研究经验（Nelly Mugo博士和Elly Katabira）。