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：
8587433
负责人：
JEANNE M MARRAZZO
金额：
$ 31.76万
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 2018-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8587433
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 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 public health relevance 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）：本提案的目的是研究避孕阴道环 (CVR) 对感染和未感染 HIV 的女性阴道细菌的影响，以及 HIV 感染女性宫颈 HIV 脱落的影响，并将这些变化与关键因素联系起来。可溶性粘膜宿主免疫防御的措施。我们将利用有限的数据来证明 CVR 对阴道细菌的有利影响，阴道细菌是抵御 HIV 和其他性传播感染 (STI) 感染的关键第一道防线。在目标 1 中，我们将确定以下效果：阴道细菌的 CVR，包括偶发性 BV 和持续性 BV。目的是研究持续阴道输送雌激素是否能促进健康阴道群体达到理想的 LB，从而降低发生和持续 BV 的风险。患有 BV 的女性将在两个月内每月进行登记和评估，以收集关键乳酸菌和 BV 相关细菌 (BVAB) 的细菌特异性定量 PCR (qPCR) 检测结果。他们将在两个月后启动 CVR，并在随后的 4 个月内每月返回进行评估。 qPCR 结果将用于确定在存在 CVR 的情况下阴道细菌浓度如何变化。我们假设 CVR 的使用与通过临床状态、Nugent 评分和 BVAB qPCR 评估的良好阴道变化相关。在目标 2 中，我们将使用 CVR 测量可溶性粘膜宿主免疫反应和宫颈内膜免疫细胞群的关键参数，包括恢复在 BV 情况下减少的保护性免疫介质，例如 SLPI、防御素、乳铁蛋白和内源性抗菌药物活性，并减少促炎细胞因子和宫颈内膜中活化 T 细胞的数量。每次就诊时都会收集宫颈内拭子、细胞刷和宫颈阴道灌洗液，并测量介质浓度和针对大肠杆菌、HIV 和 HSV-2 的抗菌活性。在目标 3 中，我们将评估参与上述程序的感染 HIV 且未接受抗逆转录病毒治疗的女性子集 (CD4>350) 在建立 CVR 之前和之后的 HIV 排出情况。我们假设 CVR 的使用将促进理想的以乳杆菌为主的非炎症性阴道环境，减少生殖器 HIV 脱落的频率和数量，从而有助于降低 HIV 传播风险。