Hormonal Contraception and HIV Acquisition: An IPD Meta-analysis

描述(由申请人提供)：撒哈拉以南非洲的妇女感染艾滋病毒的风险不成比例，使用激素避孕药的比例很高，包括注射孕激素、醋酸甲羟孕酮(DMPA)和联合口服避孕药(OCS)。了解荷尔蒙避孕对艾滋病毒感染的影响是一个关键的、尚未回答的公共卫生问题。我们建议对激素避孕(包括DMPA和OCS)和HIV感染之间的关系进行个人参与者数据(IPD)荟萃分析。具体地说，我们将评估这些荷尔蒙避孕方法是否总体上增加了育龄妇女以及包括年轻妇女(25岁)和HSV-2阴性妇女在内的重要亚群感染艾滋病毒的风险。我们将使用11项高质量前瞻性研究的数据，这些研究包括21,000多名非洲妇女和1,000例艾滋病毒感染事件，这些数据来自阴道实践研究伙伴关系(VPRP)。VPRP已经以标准格式汇编了每项研究的暴露和结果数据以及重要的协变量。我们将首先进行描述性分析，以获得对研究内部和研究之间获得的数据的详细了解。我们将使用两阶段荟萃分析来评估研究之间的异质性，并在每个研究中使用一组共同的协变量单独检查HC暴露和HIV感染之间的总体联系。然后，我们将进行Meta回归，结合总结措施，对HC对HIV感染的影响提供总体估计。我们还将使用一阶段荟萃分析方法，结合所有研究的IPD进行单一分析，以与两阶段荟萃分析的结果进行比较。一阶段方法将应用多变量COX随机效应模型，按包括其他预后因素的研究进行分层，以评估和总结不同种类的HC暴露对HIV感染的影响。IPD荟萃分析将使我们能够在研究中一致地检查激素避孕药与艾滋病毒获得的关系，同时最大化研究的力量和精确度(特别是在年轻和HSV-2阴性女性的子组中)。此外，我们应该能够更好地控制潜在的混杂变量，并评估和了解跨研究效应的异质性。拟议的荟萃分析将提供有关激素避孕对艾滋病毒感染的影响的重要信息。它为填补科学知识与迫切需要向艾滋病毒高发地区的妇女提供有效和安全的避孕措施之间的差距提供了一个重要机会。 公共卫生相关性：我们建议对荷尔蒙避孕药使用-注射孕激素DMPA和口服避孕药-与HIV感染之间的关系进行个人参与者数据荟萃分析。使用11项高质量前瞻性研究的数据，超过21,000名非洲妇女参加，我们将使用一和两个阶段的荟萃分析方法来检查激素避孕药的使用和艾滋病毒感染之间的关系，以及年轻(25岁)和HSV-2阴性妇女之间的关系。

DESCRIPTION (provided by applicant): Women in Sub-Saharan Africa are at disproportionate risk of HIV acquisition and have a high prevalence of hormonal contraceptive use including the injectable progestin, depot-medroxyprogesterone acetate (DMPA), and combined oral contraceptives (OCs). Understanding the impact of hormonal contraception on HIV acquisition is a critical unanswered public health question. We propose to conduct an individual participant data (IPD) meta-analysis of the relationship between hormonal contraception (HC) including DMPA and OCs and HIV acquisition. Specifically, we will evaluate whether or not these hormonal contraceptive methods increase the risk of HIV acquisition in women of reproductive ages overall and among important subgroups including young women (<25 years) and HSV-2 negative women. We will use data from eleven high-quality prospective studies comprising over 21,000 African women and 1,000 incident HIV infections drawn from the Vaginal Practices Research Partnership (VPRP). The VPRP has already compiled exposure and outcome data and important covariates in a standard format from each study. We will first do descriptive analyses to gain a detailed understanding of the data received within and between studies. We will use two-stage meta-analysis to assess heterogeneity between studies and to examine the overall association between HC exposures and HIV acquisition in each study individually using a common set of covariates. We will then conduct meta-regression to combine summary measures to provide an overall estimate of the HC effect on HIV acquisition. We will also use a one-stage meta-analysis approach that combines the IPD from all studies to perform a single analysis to compare with the results from the two-stage meta-analysis. The one-stage approach will apply multivariable Cox random effect models stratified by study that includes other prognostic factors to evaluate and summarize heterogeneous HC exposure effects on HIV acquisition. The IPD meta-analysis will allow us to examine the hormonal contraceptive-HIV acquisition relationship consistently across studies while maximizing study power and precision (particularly in subgroups of young and HSV-2 negative women). Additionally, we should be able to better control for potential confounding variables and assess and understand heterogeneity in effects across studies. The proposed meta-analysis will provide important information about the impact of hormonal contraception on HIV acquisition. It offers an important opportunity to fill the gap between scientific knowledge and the urgent need to provide women in high HIV prevalence areas with effective and safe contraception. PUBLIC HEALTH RELEVANCE: We propose to conduct an individual participant data meta-analysis of the relationship between hormonal contraceptive use - the injectable progestin DMPA and oral contraceptives - and HIV acquisition. Using data from eleven high-quality prospective studies in which over 21,000 African women were enrolled, we will use one and two-stage meta-analysis approaches to examine the association between hormonal contraceptive use and HIV acquisition overall and among young (<25 years) and HSV-2 negative women.