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

南非年轻女性的注射避孕药与 HIV/HSV-2 发病率

• 批准号: 8587979
• 负责人: HEENA Pushkar BRAHMBHATT
• 金额: $ 34.59万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-19 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8587979
• 关键词: AIDS prevention; Accounting; African; Attitude; Back; Behavior Control; Biological Response Modifiers; Cells; Cervical; Cessation of life; Characteristics; Chlamydia trachomatis; Cohort Studies; Collaborations; Collection; Communicable Diseases; Computer Assisted; Contraceptive Agents; Contraceptive Usage; Contraceptive methods; Data; Development; Disinhibition; Epithelium; Event; Exposure to; Faculty; Female; Future; Genital system; HIV; HIV Infections; Health; Health Personnel; Health Sciences; Health Technology; High Risk Woman; Hormonal; Hormones; Human Herpesvirus 2; Human Papillomavirus; Human immunodeficiency virus test; Human papilloma virus infection; Immune; Immunology; Incidence; Infection; Infection Control; Infection prevention; Inflammation; Injectable; Institutes; Intervention; Interview; Laboratories; Link; Medical; Menstrual cycle; Modeling; Molecular Medicine; Mucosal Immunity; Mycoplasma genitalium; Neisseria gonorrhoeae; Observational Study; Policy Maker; Population; Predisposition; Prevalence; Prevention Research; Publishing; Recurrence; Reproductive Health; Research; Risk; Risk Behaviors; Role; Safety; Sampling; Services; Sex Behavior; Sexual Health; Sexually Transmitted Diseases; South Africa; Staging; Structural Models; Structure; Survival Analysis; Swab; Technology; Testing; Time; Trichomonas vaginalis; Unwanted pregnancy; Vaccines; Vagina; Visit; Wit; Woman; age effect; aged; base; cohort; condoms; demographics; experience; hormonal contraception; male; microbicide; preference; pregnancy prevention; prevent; prospective; public health relevance; randomized trial; sex risk; sexually active; transmission process; virology; young woman

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.

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%)，其中男性到女性的艾滋病毒传播率非常高（ 2% 至 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 DMPA 等避孕注射剂 (IC) 可能会增加女性感染艾滋病毒的风险，并且这种风险在年轻女性（<20 岁）中明显更高。单纯疱疹病毒 2 (HSV-2) 已被证明与女性 HIV 感染率显着增加有关。鉴于 IC（DMPA 和 NET-EN）是南澳年轻女性最常用的避孕方法，因此我们必须有更多的经验数据来了解 IC 降低 HIV 和 HSV-2 风险的机制。我们建议根据目前使用 IC 或非 HC（避孕套、宫内节育器）的情况，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： 目标 1：IC 对 HIV 和 HIV 发病率的影响HSV-2 以及 HPV 和常见细菌性 STI 的点流行率。妇女将每 3 个月接受一次 HIV 检测，每季度收集 HSV-2、HPV 和细菌性 STI 样本，每年进行检测，并对所有阳性样本进行回溯检测，以确定感染的大致时间。目标 2：通过使用计算机辅助自我访谈，我们将在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。目标 3：将在一个月经周期中每周对一组女性 (N=30) 进行检查，以评估生殖道微生物菌群的变化以及与 IC 使用以及感染暴露相关的粘膜免疫，控制内源性激素。离散 Kaplan-Meier 曲线和时序检验将用于估计 HIV 和 HSV-2 的发病率，并按避孕措施的使用进行分层。 Cox 回归模型将用于识别基线固定协变量（IC 与非 HC）以及时间无关（人口统计学）或时间依赖性（避孕药具暴露、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）。边际结构模型将用于所有重复事件和多重事件，以解释我们研究中的时间依赖性混杂因素。在南非，性活跃的年轻女性感染 HIV 和 HSV-2 以及其他常见性传播感染的风险很高，而且大多数女性都使用 IC。这些数据将为面临性传播感染和艾滋病毒风险的妇女提供关于 IC 的安全性和有效性的指导，并协助开发将生殖健康、艾滋病毒和性传播感染预防结合起来的新的多用途生殖健康技术。