Revealing women's hidden role as critical components of HIV transmission networks in Rakai, Uganda: an interdisciplinary approach

 描述(申请人提供)：在撒哈拉以南非洲，妇女的艾滋病毒负担比男子高约60%，这种性别不平等是艾滋病毒控制的关键挑战。确定艾滋病毒风险最大的妇女及其感染艾滋病毒的男性伴侣，对于有效、有针对性地控制非洲艾滋病毒流行至关重要。确定哪些感染艾滋病毒的妇女最有可能助长持续的病毒传播也是至关重要的。然而，非洲妇女在以访谈为基础的调查和临床环境中极大地低估了性接触和性工作等高风险职业，这使得她们的身份识别具有挑战性。在这里，我们建议使用系统发生学、流行病学和定性的方法来研究乌干达拉凯区农村地区女性感染艾滋病毒并向男性传播的网络驱动因素。我们将使用Rakai社区队列研究(RCCS)的现有数据，RCCS是一项基于人口的研究，对50个社区(n~17,000)的艾滋病毒发病率和行为进行研究。在目标1中，我们将利用病毒系统发育学确定在传播网络中具有核心作用的艾滋病毒感染妇女，然后用RCCS流行病学数据描述她们的特征。我们还将对这些妇女进行深入访谈，以更深入地了解她们与艾滋病毒相关的风险，并了解报告这些风险的障碍。在目标2中，我们将使用病毒系统发育学结合概率统计模型来确定在Rakai女性中承受过多艾滋病毒负担的感染男性伴侣的池。最后，在目标3中，我们将使用微观模拟模型来评估针对高危亚群的各种组合艾滋病毒预防策略的潜在有效性，以减少艾滋病毒的发病率。这项拟议的研究是K01奖项的一部分，将为申请者提供必要的艾滋病毒建模、行为科学和系统发育学方面的高级培训，以过渡到具有将跨学科方法应用于艾滋病毒流行病学和预防方面的专业知识的独立调查员。结果将改进女性艾滋病毒风险评估，并确定预防非洲妇女艾滋病毒的候选目标战略。它还将为未来的R01提供关键的形成数据，以实施和经验性地评估对Rakai的高危妇女及其伴侣进行有针对性的干预的有效性。

 DESCRIPTION (provided by applicant): The burden of HIV is ~60% higher in women than men in sub-Saharan Africa, and this gender inequity is a key challenge to HIV control. Identifying women at greatest risk for HIV and their infecting male partners is critical for effective, targeted control of the African HIV epidemic. It is also vital to identify those HIV-infected women most likely to contribute to ongoing viral spread. However, African women vastly underreport sexual contacts and high risk occupations such as sex work in interview-based surveys and clinical settings making their identification challenging. Here, we propose to use phylogenetic, epidemiological, and qualitative methods to study network drivers of female risk of HIV acquisition and onward transmission to men in the rural Rakai District, Uganda. We will use existing data from the Rakai Community Cohort Study (RCCS), a population- based study of HIV incidence and behaviors in 50 communities (n~17,000). In Aim 1 we will identify HIV- infected women who have central roles in transmission networks using viral phylogenetics and then characterize them with RCCS epidemiological data. We will also conduct in-depth interviews with these women to gain deeper insight into their HIV-related risks and to understand the barriers to reporting these risks. In Aim 2 we will use viral phylogenetics in conjunction with probabilistic statistical models to identify the pool of infecting male partners tat sustain the excess HIV burden among Rakai women. Lastly, in Aim 3 we will use microsimulation models to estimate the potential effectiveness of various combination HIV prevention strategies targeted to high risk subgroups to reduce HIV incidence. The proposed research is part of a K01 award and will provide the applicant with the advanced training in HIV modelling, behavioral science, and phylogenetics necessary to transition to an independent investigator with expertise in the application of interdisciplinary methods to HIV epidemiology and prevention. Results will improve female HIV risk assessment and identify candidate targeted strategies to prevent HIV in African women. It also will provide critical formative data fr a future R01 to implement and empirically assess the effectiveness of targeted interventions to high risk women and their partners in Rakai.