Women's Life Events & HIV Transmission Potential: A Multidisciplinary Study

描述（由申请人提供）：2009年估计有260万新的艾滋病毒感染者，世界距离实现联合国艾滋病规划署零新感染的宏伟目标还有很长的路要走。在这种情况下，预防HIV-1传播已被确定为2012财年跨NIH艾滋病研究的首要任务。在最近的观察和随机试验证据表明，提供给艾滋病毒阳性个体的治疗可以减少高达96%的病毒传播给他们的性伴侣之后，迫切需要一种新的范式，重新定义我们对传播潜力的理解，因为它同时涉及性风险行为和ART暴露。艾滋病毒抗体阳性妇女现在可以预期在终身治疗的情况下延长生存期，这就需要了解在整个生命周期中传播潜力如何与关键的生殖健康事件有关，包括避孕、生育愿望、怀孕、产后期和绝经期（以下称为生命周期事件）。我们的目标是在这个多学科系列的定量和定性研究的特点的存在，规模和上下文的基础上，艾滋病毒阳性肯尼亚妇女的传播潜力的变化，这些重要的生命过程中的事件。一项前瞻性队列设计，收集补充行为和生物学终点，将提供强有力的证据，说明生命过程事件和传播潜力之间存在相关性和相关性的时间顺序，传播潜力定义为在晚期ART再灌注环境中的无保护性行为。开放队列研究将包括360名在蒙巴萨和内罗毕接受抗逆转录病毒治疗的艾滋病毒阳性肯尼亚妇女。招募的参与者将代表三个不同的重要风险群体：夫妻关系不和的妇女、妇幼保健诊所的孕妇和产后妇女以及女性性工作者。这种多样性将提供大量的普遍性，以及一个机会，以确定三个风险群体之间的传播潜力的重要差异。深入访谈和焦点小组讨论将增加我们对行为变化的社会行为背景的理解。我们能够利用从蒙巴萨艾滋病毒阳性妇女队列中持续收集的数据，这提供了一个独特的优势，因为这将使我们能够评估研究人群中一个子集在10多年内传播潜力的变化。这些研究将提供最全面的数据，以了解在艾滋病毒阳性的非洲妇女接受抗逆转录病毒治疗的传播潜力。这项研究将直接改善公共卫生，扩大我们的艾滋病毒预防的角度认识到艾滋病毒阳性的妇女的生殖生命过程事件对他们的传播潜力的潜在深远影响的理解。预计这些数据将指导计划的实施，并为新一代临床试验的开发提供信息，以优化预防，在这个时代，有效使用ART将与避孕套和禁欲一起作为预防阳性的基石。

DESCRIPTION (provided by applicant): With an estimated 2.6 million new HIV infections in 2009, the world remains a long way from reaching the ambitious UNAIDS goal of zero new infections. In this context, prevention of HIV-1 transmission has been identified as a top Fiscal Year 2012 Trans-NIH AIDS Research Priority. In the wake of recent observational and randomized trial evidence that treatment provided to HIV-positive individuals can reduce transmission of the virus to their sex partners by as much as 96%, there is an urgent need for a new paradigm that redefines our understanding of transmission potential as it relates simultaneously to both sexual risk behavior and ART exposure. For HIV-positive women, who can now anticipate prolonged survival in the context of lifelong treatment, this will require an understanding of how transmission potential varies across the lifespan in relation to key reproductive health events including decisions about contraception, fertility desire, pregnancy, the post partum period, and menopause (hereafter, lifecourse events). Our objective in this multidisciplinary series of quantitative and qualitative studies is to characterize the presence, magnitude, and contextual basis of variations in HIV-positive Kenyan women's transmission potential in relation to these important lifecourse events. A prospective cohort design with collection of complementary behavioral and biological endpoints will provide strong evidence regarding the presence and temporal sequence of associations between lifecourse events and transmission potential, defined as unprotected sex in the setting of late ART refills. The open cohort study will include 360 HIV-positive Kenyan women who are offered ART in Mombasa and Nairobi. Participants will be recruited to represent three distinct and important risk groups; women in discordant couples, pregnant and post-partum women from maternal and child health clinics, and female sex workers. This diversity will provide substantial generalizability, as well s an opportunity to identify important differences in transmission potential between the three risk groups. In-depth interviews and focus group discussions will add to our understanding of the sociobehavioral context for changes in behavior. Our ability to leverage ongoing data collection from a cohort of HIV-positive women in Mombasa provides a unique advantage, as this will allow us to evaluate changes in transmission potential over more than 10 years in a subset of the study population. These studies will provide the most comprehensive data available to understand transmission potential in HIV-positive African women treated with ART. This research will directly improve public health, expanding our understanding of HIV prevention from a perspective that recognizes the potentially profound influence of HIV-positive women's reproductive lifecourse events on their transmission potential. These data are expected guide program implementation and inform development of a new generation of clinical trials to optimize prevention in an era where effective use of ART will take its place alongside condoms and abstinence as a cornerstone of prevention in positives.