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: 9207354
• 负责人: HEENA Pushkar BRAHMBHATT
• 金额: $ 37.24万
• 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/9207354
• 关键词: AIDS prevention; Attitude; Back; Behavior Control; Biological Response Modifiers; Cells; Cervical; Cessation of life; Characteristics; Chlamydia trachomatis; 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; Hormones; Human Herpesvirus 2; Human Papillomavirus; Human immunodeficiency virus test; Human papilloma virus infection; Immune; Immunology; Incidence; Infection; 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; Prospective cohort study; Publishing; Recurrence; Reproductive Health; Research; Risk; Risk Behaviors; Role; Safety; Sampling; Services; Sex Behavior; Sexual Health; Sexually Transmitted Diseases; South Africa; South African; Structural Models; Structure; Survival Analysis; Swab; Technology; Testing; Thinness; Time; Trichomonas vaginalis; Unwanted pregnancy; Vaccines; Vagina; Visit; Wit; Woman; age effect; aged; base; cohort; condoms; demographics; experience; hormonal contraception; male; microbicide; microbiota; preference; pregnancy prevention; prevent; prospective; public health relevance; randomized trial; reproductive tract; 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）：南非的年轻女性（SA）的艾滋病毒患病率最高（16-30％）和世界上的发病率（3至5％），男性至女性HIV传播率很高（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，仅凭风险行为不能解释这些高率。最近的观察性研究表明，荷尔蒙避孕（HC），特别是可注射的避孕药（IC）（例如DMPA）可能会增加女性艾滋病毒传播的风险，而在年轻女性（<20岁）中，这种风险大大更高。单纯疱疹病毒-2（HSV-2）已被证明与女性艾滋病毒感染显着增加有关。鉴于ICS（DMPA和Net-EN）是SA中年轻女性中最常用的避孕方法，因此我们有更多的经验数据来理解ICS修改HIV和HSV-2风险的机制。我们建议根据当前使用ICS或非HCS（避孕套，IUD）对600名16至24岁的性活跃女性进行一项前瞻性队列研究，以评估：AIM 1：IC对HIV和HSV-2的影响以及HPV和HPV和普通细菌性STI的影响。将每3个月对妇女进行每3个月的HIV测试，HSV-2，HPV和细菌性传播感染的样本将每季度收集，每年进行测试，所有阳性样品将进行后退测试以确定感染的近似时间。 AIM 2：通过使用计算机辅助自我意见，我们将在每季度访问期间从所有妇女那里收集敏感的性行为信息（n = 600），并评估IC和相关风险行为的影响。 AIM 3：一部分女性（n = 30），每周间隔一个月经周期，以评估生殖道微菌群的变化，以及与IC使用以及暴露于感染相关的粘膜免疫，以控制内源荷尔蒙的变化。离散的Kaplan-Meier曲线和对数秩检验将用于估计艾滋病毒和HSV-2的发病率，并通过避孕药使用进行分层。 COX回归模型将用于鉴定基线时固定协变量的影响（IC与非HC），以及时间无关（人口统计学）或时间依赖性（避孕剂暴露，生殖器结构的变化，免疫细胞，性行为）协变量。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）。边缘结构建模将用于所有复发和多个事件，以解释我们研究中时间依赖的混杂。在南非，年轻的性活跃妇女患HIV和HSV-2感染以及其他常见性传播感染以及大多数使用ICS的风险很高。这些数据将提供有关ICS对处于性传播感染和HIV风险的女性的安全性和功效的指导，并协助开发新的多功能生殖健康技术，这些健康技术结合了生殖健康，HIV和STI预防。