DMPA use and vaginal bacterial diversity among African women

项目摘要 避孕药醋酸甲羟孕酮(DMPA)与女性增多有关 通过未知的机制获得艾滋病毒。我们假设DMPA的使用增加了阴道的种类 多样性，以促进生殖器炎症和女性艾滋病毒的方式改变阴道微生物区系 收购。 我们将使用之前从81名产后肯尼亚人中收集的阴道拭子样本 发起DMPA的女性和25名使用非激素避孕的对照队列女性。 与弗雷德·哈钦森癌症研究中心的弗雷德里克斯实验室合作，这些 实验室的方法是首创的，我们将利用阴道微生物群的纵向变化来确定 大范围聚合酶链式反应和高通量测序。我们将使用分类单元特异的定量PCR来确定 记录12种最常见的阴道细菌的数量，并跟踪它们随时间的变化。然后我们将相互关联 阴道微生物区系随DMPA峰值水平的变化，并评估DMPA对特定人群的影响 阴道厌氧菌与艾滋病毒感染有关。 这里提出的工作利用专门收集的现有样本来评估生物 DMPA使用的后果，并将使用广泛的社会人口学和临床元数据来执行 比较微生物区系物种、丰富度和多样性动态变化的多元统计分析 对混杂因素进行适当调整。 如果这项研究揭示了与DMPA相关的微生物区系的显著变化，我们的结果将适用于 正在努力创造更安全的多用途艾滋病毒预防技术，并努力改善阴道健康 在撒哈拉以南非洲。

Project Summary Depot-medroxyprogesterone acetate (DMPA), a contraceptive, has been associated with increased female acquisition of HIV through unknown mechanisms. We hypothesize that DMPA use increases vaginal species diversity, changing the vaginal microbiota in ways that promote genital inflammation and female HIV acquisition. We will use previously-collected vaginal swab samples from a prospective cohort of 81 postpartum Kenyan women who initiated DMPA and a control cohort of 25 women using non-hormonal contraception. Collaborating with the Fredricks laboratory at Fred Hutchinson Cancer Research Center, where these laboratory methods were pioneered, we will determine longitudinal changes in the vaginal microbiome using broad-range PCR with high-throughput sequencing. We will use taxon-specific quantitative PCR to determine quantities of the 12 most common vaginal bacteria and track their change over time. We will then correlate vaginal microbiota changes with peak DMPA levels, and assess the impact of DMPA on specific populations of vaginal anaerobes linked to HIV acquisition. The work proposed here leverages existing specimens collected specifically to assess biological consequences of DMPA use, and will use extensive socio-demographic and clinical metadata to perform multivariate statistical analyses comparing dynamic changes in microbiota species, richness and diversity with appropriate adjustment for confounding factors. Should this research reveal significant DMPA-related microbiota changes, our results would be applicable to ongoing efforts to create safer multi-purpose HIV prevention technologies and efforts to improve vaginal health in sub-Saharan Africa.