Assessing vaginal microbial communities as a risk factor for HIV acquisition in pregnant and postpartum Kenyan women

项目摘要 与非怀孕妇女相比，怀孕和产后妇女感染艾滋病毒的风险大大增加 女人。在这段时间内，性行为的改变并不能完全解释这种风险。中的更改 阴道微生物区系和粘膜免疫激活可能为这种增加提供了一种机制 敏感度。妊娠和产后对阴道细菌浓度影响最大 与艾滋病毒感染密切相关的问题尚不清楚。解决这个问题的一个重要障碍是 研究阴道微生物区系作为HIV风险因素的最佳方法尚未确定 已经成立了。在这项建议中，候选人将首先利用物种- 从我们现有的HIV获取数据集中提取特定的定量聚合酶链式反应数据以生成阴道细菌图谱 根据20种细菌分类群的集体浓度描述不同的妇女群体，包括 与艾滋病毒感染关系最密切的少数民族物种。然后，考生将参加考试 不同细菌类型与艾滋病毒感染之间的联系(目标1)。来自AIM 1的数据将提供信息 目标2和目标3中的分析，利用产后队列中正在进行的先入为主的独特数据 肯尼亚内罗毕。这些分析将检查关键阴道细菌物种的浓度(目标2)和 与艾滋病毒风险相关的粘膜细胞因子浓度(目标3)在先入为主的过程中演变， 孕期和产后期。我们推测阴道细菌谱的特征是 “高危”阴道细菌群的浓度将与女性感染艾滋病毒的风险相关。 此外，我们预计与艾滋病毒感染相关的阴道细菌浓度将在 妊娠期和产后期与未孕相比。我们的结果可能会为HIV的发展提供信息 针对阴道微生物区系的预防策略，并提供有关这些干预措施如何实施的见解 为怀孕和产后量身定做。这项拟议的研究计划伴随着强有力的培训 计划包括几个领域的正规和非正规教育，包括：1)利用尖端技术进行分析 实验室数据，包括宫颈阴道分泌物中阴道微生物区系的分子定量，2) 使用先进的统计方法处理高维阴道微生物区系数据，3)内容物 艾滋病毒预防领域的知识，特别侧重于妇女的关键易感时期 生殖生活--怀孕和产后，以及4)职业发展机会，包括赠款申请 和指导经验。候选人的长期职业目标是利用她在生物方面的培训，应用 公共卫生和流行病学进行高影响力的研究，为改善 妇女的性健康和生殖健康，如艾滋病毒感染、生育和流产。这些知识和知识 在F32奖学金期间培养的技能将为候选人成功进行独立研究做好准备 从事这项重要工作的职业。

PROJECT ABSTRACT Pregnant and postpartum women are at substantially increased risk of HIV acquisition compared to non-pregnant women. The risk is not fully explained by changes in sexual behavior during these time periods. Alterations in the vaginal microbiota and mucosal immune activation may provide a mechanism for this increased susceptibility. The impact of pregnancy and the postpartum period on concentrations of the vaginal bacteria most strongly associated with HIV acquisition is unknown. One important barrier to addressing this question is that the optimal approach for investigating vaginal microbiota as a risk factor for HIV has not been definitively established. In this proposal, the candidate will first perform hierarchical clustering analysis utilizing species- specific quantitative PCR data from our existing HIV acquisition dataset to generate vaginal bacterial profiles describing distinct groups of women based on the collective concentrations of 20 bacterial taxa, including the minority species that have been most closely associated with HIV acquisition. The candidate will then examine the association between the distinct bacterial profiles and HIV acquisition (Aim 1). Data from Aim 1 will inform analyses in Aims 2 and 3, utilizing unique data from an ongoing preconception through postpartum cohort in Nairobi, Kenya. These analyses will examine how concentrations of key vaginal bacterial species (Aim 2) and concentrations of mucosal cytokines (Aim 3) associated with HIV risk evolve over the course of preconception, pregnancy, and the postpartum period. We hypothesize that vaginal bacterial profiles characterized by high concentrations of groups of ‘high-risk’ vaginal bacteria will be associated with women’s risk of HIV acquisition. In addition, we expect that concentrations of vaginal bacteria associated with HIV acquisition will be higher during pregnancy and the postpartum period compared to preconception. Our results could inform development of HIV prevention strategies targeting the vaginal microbiota and provide insight on how these interventions might be tailored for pregnancy and the postpartum period. This proposed research plan is paired with a robust training plan encompassing formal and informal education in several areas including: 1) analysis utilizing cutting-edge laboratory data, including molecular quantification of vaginal microbiota in cervicovaginal secretions, 2) employing advanced statistical methods to contend with highly dimensional vaginal microbiota data, 3) content knowledge in the field of HIV prevention, with a specific focus on key vulnerable periods in a woman’s reproductive life – pregnancy and postpartum, and 4) career development opportunities including grant writing and mentoring experience. The candidate’s long-term career goal is to leverage her training in biology, applied public health, and epidemiology to conduct high-impact research that informs interventions for improving women’s sexual and reproductive health such as HIV acquisition, fertility, and miscarriage. The knowledge and skills developed during the F32 Fellowship will prepare the candidate for a successful independent research career conducting this important work.