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

评估阴道微生物群落作为肯尼亚孕妇和产后妇女感染艾滋病毒的危险因素

• 批准号: 10291403
• 负责人: Erica M Lokken
• 金额: $ 2.31万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-11-01 至 2022-01-07
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10291403
• 关键词: AIDS prevention; Address; African; Area; Bacteria; Biology; Cells; Cluster Analysis; Communities; Data; Data Set; Development; Dimensions; Epidemiologic Methods; Epidemiology; Fellowship; Fertility; First Pregnancy Trimester; Genital; Genitalia; Goals; Grant; HIV; HIV Infections; HIV risk; Individual; Inflammation; Inflammatory; Intervention; Kenya; Knowledge; Laboratories; Lactobacillus; Lead; Life; Mechanics; Mediating; Mentors; Minority; Molecular; Mucous Membrane; Pattern; Postpartum Period; Postpartum Women; Predisposition; Pregnancy; Pregnant Women; Prevention strategy; Prospective Studies; Public Health; Reproductive Health; Reproductive Periods; Research; Risk; Risk Factors; Role; Sex Behavior; Sexual Health; Spontaneous abortion; Statistical Methods; Third Pregnancy Trimester; Time; Training; Vagina; Woman; Women' s Group; Work; Writing; bacterial community; base; career; career development; case control; cervicovaginal; cohort; cytokine; experience; high risk; high risk population; immune activation; improved; informal learning; insight; microbial community; novel; novel strategies; pregnant; recruit; reproductive; reproductive tract; skills; trying to conceive; vaginal microbiota; vaginal mucosa

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.

项目摘要 与非孕妇相比，孕妇和产后妇女感染艾滋病毒的风险大大增加 妇女这种风险不能完全用这些时间段内性行为的变化来解释。的改变 阴道微生物群和粘膜免疫激活可能提供了这种增加的机制， 易感性怀孕和产后对阴道细菌浓度的影响最大 与艾滋病病毒感染密切相关的是未知的。解决这一问题的一个重要障碍是， 研究阴道微生物群作为HIV风险因素的最佳方法尚未确定 确立了习在这个提议中，候选人将首先利用物种进行层次聚类分析- 从我们现有的HIV采集数据集获得特异性定量PCR数据，以生成阴道细菌谱 基于20种细菌分类群的集体浓度描述了不同的妇女群体，包括 少数物种与艾滋病毒感染关系最密切。然后，候选人将检查 不同细菌谱与HIV感染之间的关联（目标1）。目标1的数据将告知 目的2和3中的分析，利用来自持续孕前至产后队列的独特数据， 肯尼亚，内罗毕。这些分析将检查关键阴道细菌种类（目标2）和 与HIV风险相关的粘膜细胞因子浓度（Aim 3）在孕前过程中演变， 妊娠期和产后期。我们假设，阴道细菌谱特征为高 “高危”阴道细菌群的浓度将与妇女感染艾滋病毒的风险有关。 此外，我们预计，与艾滋病毒感染相关的阴道细菌浓度在感染期间会更高。 怀孕和产后期与孕前相比。我们的研究结果可以为艾滋病毒的发展提供信息 针对阴道微生物群的预防策略，并提供关于这些干预措施如何 专为怀孕和产后时期量身定制。这项拟议的研究计划与一项强有力的培训相结合， 一项涵盖正规和非正规教育的计划，涉及以下几个领域： 实验室数据，包括宫颈阴道分泌物中阴道微生物群的分子定量，2） 采用先进的统计方法来处理高维阴道微生物群数据，3）内容 艾滋病毒预防领域的知识，特别侧重于妇女生命中的关键脆弱时期， 生育期-怀孕和产后，以及4）职业发展机会，包括撰写赠款 和指导经验。候选人的长期职业目标是利用她在生物学，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。的知识和 在F32奖学金期间开发的技能将为候选人成功的独立研究做好准备 从事这项重要工作。