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

描述（由申请人提供）：南非（SA）的年轻女性正在经历世界上最高的艾滋病毒流行率（16-30%）和发病率（3 - 5%），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预防研究的重点，但很明显，这些高感染率不能仅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（ICs），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。2型单纯疱疹病毒（HSV-2）已被证明与妇女感染艾滋病毒的显著增加有关。鉴于ic （DMPA和NET-EN）是南非年轻女性中最常用的避孕方法，我们有更多的经验数据来了解ic改变HIV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一项前瞻性队列研究，基于目前使用避孕措施或非避孕措施（避孕套，宫内节育器），以评估：目的1：避孕措施对HIV和HSV-2的发病率以及HPV和常见细菌性性传播感染的点患病率的影响。妇女将每3个月进行一次艾滋病毒检测，每季度收集一次2型单纯疱疹病毒、人乳头瘤病毒和细菌性传播感染的样本，每年进行一次检测，并对所有阳性样本进行回测，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，我们将在每季度访问期间收集所有女性（N=600）的敏感性行为信息，并评估IC和相关风险行为的影响。目的3：一组妇女（N=30）将在一个月经周期内每周观察一次，以评估与IC使用和感染暴露相关的生殖道微生物群和粘膜免疫的变化，控制内源性激素的变化。将使用离散Kaplan-Meier曲线和log-rank检验来估计HIV和HSV-2的发病率，并按避孕措施的使用分层。Cox回归模型将用于确定基线固定协变量（IC与非hc）、时间无关（人口统计学）或时间相关（避孕暴露、生殖器结构变化、免疫细胞、性行为）协变量的影响。生存分析将用于评估IC对HIV进展的影响（死亡时间、CD4下降等）。在我们的研究中，边际结构建模将用于所有周期性和多重事件，以解释与时间相关的混淆。在南非，性活跃的年轻妇女感染艾滋病毒和2型单纯疱疹病毒以及其他常见性传播感染的风险很高，其中大多数人使用注射性药物。这些数据将为有感染性传播感染和艾滋病毒风险的妇女提供关于免疫注射的安全性和有效性的指导，并协助开发结合生殖健康、艾滋病毒和性传播感染预防的新的多用途生殖健康技术。

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.