Effects of contraceptive ring on vaginal microbiota, HIV shedding and local immun

描述（由申请人提供）：本提案的目的是研究避孕阴道环（CVR）对感染HIV和未感染HIV的女性阴道细菌和HIV感染女性宫颈HIV脱落的影响，并将这些变化与可溶性粘膜宿主免疫防御的关键措施联系起来。我们将以有限的数据为基础，表明CVR对阴道细菌的有利作用，阴道细菌是抵御艾滋病毒感染和其他性传播感染（STI）的关键第一道防线。在目标1中，我们将确定的效果

DESCRIPTION (provided by applicant): The objective of this proposal is to study effects of a contraceptive vaginal ring (CVR) on vaginal bacteria in women with and without HIV, and cervical HIV shedding in HIV-infected women, and relates these changes to key measures of soluble mucosal host immune defense. We will build on limited data suggesting a favorable effect of CVR on vaginal bacteria, which comprise a critical first line of defense against infectio with HIV and other sexually transmitted infections (STI). In Aim 1, we will determine the effect of the CVR on vaginal bacteria, including incident and persistent BV. The goal is to study whether sustained vaginal delivery of estrogen promotes healthy vaginal populations of desirable LB, and thus reduces risk of incident and persistent BV. Women with BV will be enrolled and assessed monthly for two months to collect bacterium-specific quantitative PCR (qPCR) assays for key lactobacilli and BV- associated bacteria (BVAB). They will initiate CVR after two months and will return monthly over 4 subsequent months for assessment. qPCR results will be used to determine how concentrations of vaginal bacteria change in presence of absence of CVR. We hypothesize that CVR use will be associated with favorable vaginal change assessed by clinical status, Nugent score, and BVAB qPCR. In Aim 2, we will measure key parameters of the soluble mucosal host immune response and endocervical immune cell populations with CVR use, including restoration of protective immune mediators that are decreased in the setting of BV such as SLPI, defensins, lactoferrrin, and endogenous antimicrobial activity, and reduction in pro-inflammatory cytokines and the number of activated T-cells in the endocervix. Endocervical swabs, cytobrushes and cervicovaginal lavage will be collected at each visit and concentrations of mediators and antimicrobial activity against E. coli, HIV and HSV-2 measured. In Aim 3, we will evaluate HIV shedding prior to and after establishment of the CVR in a subset of women enrolled in the above procedures who are HIV-infected and not on antiretroviral therapy (CD4>350). We hypothesize that CVR use will promote a desirable Lactobacillus- predominant, non-inflammatory vaginal environment with reduced frequency and quantity of genital HIV shedding, thereby contributing to a reduction of HIV transmission risk.