Injectable Contraception and HIV/HSV-2 Incidence in Young South African Women

描述(由申请人提供)：南非(SA)年轻女性的艾滋病毒感染率(16%-30%)和发病率(3%-5%)是世界上最高的，男性对女性的艾滋病毒传播率非常高(2%-6%)。尽管性行为一直是艾滋病毒预防研究的重点，但很明显，这些高发病率不能仅用危险行为来解释。最近的观察性研究发现，激素避孕(HC)，特别是注射避孕药(IC)，如DMPA，可能会增加妇女感染艾滋病毒的风险，这种风险在年轻妇女(20岁)中明显更高。单纯疱疹病毒-2(HSV-2)已被证明与妇女艾滋病毒感染的显著增加有关。鉴于ICs(DMPA和Net-EN)是SA年轻女性最常用的避孕方法，我们有更多的经验数据来理解ICs改变艾滋病毒和HSV-2风险的机制是至关重要的。我们建议对600名16至24岁的性活跃女性进行前瞻性队列研究，以评估IC和非HCS(避孕套，IUD)的当前使用情况，以评估：目的1：IC对HIV和HSV-2的发病率以及HPV和常见细菌性传播感染的现患率的影响。每3个月将对妇女进行艾滋病毒检测，并将每季度收集HSV-2、HPV和细菌性传播疾病样本，每年进行测试，并对所有阳性样本进行重新测试，以确定感染的大致时间。目的2：通过使用计算机辅助的自我访谈，我们将收集所有女性(N=600)在季度访问期间的敏感性行为信息，并评估IC及相关危险行为的影响。目的3：一组妇女(N=30)每周观察一次月经周期，以评估生殖道微生物区系的变化，以及与IC使用和暴露于感染相关的粘膜免疫，以控制内源性激素的变化。离散的Kaplan-Meier曲线和对数等级检验将被用来估计HIV和HSV-2的发病率，并按避孕措施的使用进行分层。COX回归模型将被用来确定基线(IC与非HC)的固定协变量以及时间无关(人口统计学)或时间依赖(避孕措施暴露、生殖器结构、免疫细胞、性行为的变化)协变量的影响。生存分析将用于评估IC对HIV进展(死亡时间、CD4下降等)的影响。在我们的研究中，所有重复和多重事件的边际结构模型将被用来解释时间依赖的混杂。在南非，年轻的性行为活跃的妇女感染艾滋病毒和HSV-2以及其他常见的性传播感染的风险很高，而且大多数人使用IC。这些数据将为性传播感染和艾滋病毒高危妇女接受免疫接种的安全性和有效性提供指导，并有助于开发结合生殖健康、艾滋病毒和性传播感染预防的多用途生殖健康新技术。

DESCRIPTION (provided by applicant): Young women in South Africa (SA) are experiencing the highest HIV prevalence (16-30%) and incidence (3 to 5%) rates in the world, with very high male to female HIV transmission rates (2 to 6%). Although sexual behaviors have been the focus of HIV prevention research, it is clear that these high rates cannot be explained by risk behaviors alone. Recent observational studies have identified that hormonal contraception (HC), and in particular injectable contraceptive (ICs) such as DMPA may increase the risk of HIV transmission in women and this risk is significantly higher in younger women (<20 years). Herpes Simplex Virus-2 (HSV-2), has been shown to be associated with a significant increase in HIV infection in women. Given that ICs (DMPA and NET-EN) are the most commonly used contraception among young women in SA, it is critical we have more empirical data to understand the mechanism by which ICs modify the risk of HIV and HSV-2. We propose to conduct a prospective cohort study among 600 sexually active women aged 16 to 24 years based on current use of ICs or non-HCs (condoms, IUD) so as to assess: Aim 1: the impact of IC on incidence of HIV and HSV-2 and point prevalence of HPV and common bacterial STIs. Women will be tested for HIV every 3 months and samples for HSV-2, HPV and bacterial STIs will be collected quarterly, tested annually and all positive samples will be back-tested to ascertain the approximate time of infection. Aim 2: Through the use of computer assisted self-interviews, we will collect sensitive sexual behavior information from all women (N=600) during quarterly visits and assess impact of IC and associated risk behaviors. Aim 3: A subset of women (N=30), will be seen at weekly intervals for one menstrual cycle to assess changes in genital tract micro flora, and mucosal immunity associated with IC use as well as exposure to infections, controlling for changes in endogenous hormones. Discrete Kaplan-Meier curves and log-rank tests will be used to estimate the incidence rates of HIV and HSV-2, stratified by contraceptive use. Cox regression models will be used to identify effects for fixed covariates at baseline (IC versus non-HC), and time-independent (demographics) or time-dependent (contraceptive exposure, changes in genital structure, immune cells, sexual behavior) covariates. Survival analyses will be used to assess the impact of IC on HIV progression (time to death, CD4 decline, etc.). Marginal structural modeling will be used for all recurrent and multiple events to account for the time-dependent confounding in our study. In South Africa, young sexually active women are at high risk for HIV and HSV-2 infection, as well as other common STIs, and a majority use ICs. These data will provide guidance on the safety and efficacy of ICs for women at risk for STIs and HIV, and assist in the development of new multi-purpose reproductive health technologies that combine reproductive health, HIV and STI prevention.