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

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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.