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

避孕环对阴道微生物群、HIV 排出和局部免疫的影响

基本信息

批准号：
8922957
负责人：
JEANNE M MARRAZZO
金额：
$ 45.56万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-15 至 2016-02-15
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8922957
关键词：
Advocate Africa Africa South of the Sahara Anaerobic Bacteria Bacteria Bacterial Vaginosis Biological Assay Biological Response Modifiers Cells Cervical Clinical Collection Communities Contraceptive Agents Contraceptive methods Data Defensins Endocervix Enrollment Environment Escherichia coli Estrogens Etiology Flow Cytometry Frequencies Genital system Goals HIV HIV Infections HIV risk Health Hormonal Hormones Host Defense Human Herpesvirus 2 Human Milk Hydrogen Peroxide Immune Immune response Immunity Immunology procedure Infection Inflammation Inflammatory Intervention Irrigation Lactobacillus Measures Mediator of activation protein Methods Molecular Outcome Pathway interactions Pelvic Inflammatory Disease Perinatal Population Pregnancy Pregnancy Outcome Prevention Procedures Progesterone Prophylactic treatment RNA Risk Scientist Sexually Transmitted Diseases Simplexvirus Site Swab T-Lymphocyte Time Vagina Vaginal Ring Vaginal delivery procedure Vaginitis Viral Visit Woman antileukoprotease antimicrobial antiretroviral therapy cervicovaginal chemokine cytokine human SLPI protein local drug delivery male microbial community novel pregnancy prevention prevent pyrosequencing rRNA Genes reproductive response restoration tool transmission process unintended pregnancy vaginal lactobacilli

项目摘要

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.

描述（由申请人提供）：该提案的目的是研究避孕阴道环（CVR）对患有和没有HIV的妇女的阴道细菌的影响，以及在受HIV感染的妇女中的宫颈HIV脱落，并将这些变化与关键联系起来可溶性粘膜宿主免疫防御的度量。我们将基于有限的数据建立，这表明CVR对阴道细菌产生了有利的影响，该数据构成了针对HIV和其他性传播感染（STI）对感染感染的关键第一道防线。在AIM 1中，我们将确定阴道细菌的CVR，包括入射和持续性BV。目的是研究雌激素的阴道持续分娩是否促进了所需LB的健康阴道种群，从而降低了出现和持续性BV的风险。患有BV的妇女将每月注册并评估两个月，以收集细菌特异性定量PCR（QPCR）测定法，以进行关键的乳酸乳杆菌和BV-相关细菌（BVAB）。他们将在两个月后启动CVR，并将在随后的4个月内每月返回评估。 QPCR结果将用于确定在不存在CVR的情况下，阴道细菌的浓度如何变化。我们假设CVR使用将与通过临床状况，Nugent评分和BVAB QPCR评估的有利的阴道变化有关。在AIM 2中，我们将测量可溶性粘膜宿主免疫反应的关键参数和使用CVR使用的宫颈免疫细胞群体，包括恢复BV，例如SLPI，Defensins，defensins，lactoferrrin和内源性抗菌剂等BV中降低的保护性免疫介质的恢复活性和促炎细胞因子的降低以及内胚中活化的T细胞的数量。每次访问和介体的浓度以及针对大肠杆菌，HIV和HSV-2的抗菌活性，将收集宫颈拭子，细胞刷和宫颈阴道灌洗。在AIM 3中，我们将评估在CVR之前和建立CVR之前和之后的艾滋病毒脱落，其中包括接受HIV感染且不接受抗逆转录病毒治疗的女性（CD4> 350）。我们假设CVR使用将促进理想的乳杆菌 - 主要的非炎性阴道环境，其频率和生殖器HIV脱落的频率和数量降低，从而有助于降低HIV传播风险。