“Inflammation, Vaginal Microbiota, and STI/HIV Risk”

– 炎症、阴道微生物群和 STI/HIV 风险 –

基本信息

批准号：
9908138
负责人：
Jenell S Coleman
金额：
$ 47.27万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-04-03 至 2023-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9908138
关键词：
16S ribosomal RNA sequencing AIDS prevention Address Adhesives Adolescent Adolescent and Young Adult Adult Anaerobic Bacteria Anatomy Anti-Infective Agents Bacterial Vaginosis Biological Biological Factors Biomedical Technology Cells Coitus Communities Complex Contraceptive Agents Data Defense Mechanisms Development Energy-Generating Resources Environment Epithelial Epithelium Estrogens Female Female Adolescents Glucocorticoids Glycogen Goals HIV HIV Infections HIV risk High Prevalence Hormonal Hormones Host Defense Mechanism Immune Immunity Impairment Inflammation Inflammatory Injectable Intervention Intrauterine Devices Knowledge Lactic acid Lactobacillus Lead Measures Medroxyprogesterone 17-Acetate Methods Mucous Membrane Mucous body substance Observational Study Physiology Population Predisposition Pregnancy in Adolescence Progestins Property Proteins Public Health Reporting Research Risk Role STI prevention Sexually Transmitted Diseases Social Behavior Surface Swab Symptoms Testing Time Vagina Woman aged antimicrobial boys cervicovaginal chemokine co-infection condoms cytokine design girls high risk high school hormonal contraception immune function improved innovation insight microbiota novel strategies pathogen prospective recruit reproductive hormone reproductive tract sexually active sexually active adolescent synergism unintended pregnancy vaginal microbiota young adult young man young woman

项目摘要

Young people (15-24 years old [yo]) acquire half of the 20 million new sexually transmitted infections (STI) annually in the U.S. and 1 in 4 sexually active adolescent girls has an STI. Complex biological, socio- behavioral, and cultural factors place sexually active adolescent girls at higher risk of acquiring STIs compared with boys and adult women. Some STIs can increase HIV acquisition by breaching the protective mucosal epithelial barrier, promoting inflammation, and recruiting HIV target cells into the genital tract. This synergy between STIs, inflammation, and HIV contributes to the 380,000 new HIV infections among adolescent girls and young women (10-24yo) each year worldwide. In communities where STI and HIV prevalence are high, sexually active girls using hormonal contraception (HC), but without barrier protection, are at risk of STI/HIV acquisition. Several observational studies have suggested that depot medroxyprogesterone acetate (DMPA) may increase the risk of HIV acquisition by up to 3.0-fold. Yet, the biological aspects of STI co-infections, inflammation, exogenous hormones, and HIV acquisition in adolescent girls and young women are understudied. Given that most HIV infections occur at mucosal surfaces, there is a critical need to better understand mucosal immune function and biologic factors like hormonal status and vaginal microbiota that can alter susceptibility to STI/HIV among adolescent girls and young women. In the absence of such knowledge, the development of effective biomedical technologies to prevent STIs and HIV within this vulnerable key population will likely remain difficult. Our central hypothesis is that the hypoestrogenemia induced by DMPA decreases the vagina's natural host defense mechanisms against STI/HIV by altering the microbiota (e.g. decreasing lactobacilli), decreasing mucus pathogen trapping properties, and increasing inflammation. To test our hypothesis, we propose the following two specific aims: (1) To identify the association between the vaginal microbiota, inflammation, and STIs. The vaginal microbiota of 225 menarcheal, sexually-active, healthy U.S. adolescent girls and young women (13-24yo) will be characterized by 16s rRNA sequencing using self- collected vaginal swabs in a cross-sectional design; and (2) To determine the impact of DMPA use on vaginal microbiota, inflammation, and female genital tract anatomy and physiology. A subset of adolescent girls and young women who initiate DMPA (n=40) or those not using any HC (n=40) will be followed prospectively. Changes from baseline in the vaginal microbiota, inflammation, and cervicovaginal mucus properties will be assessed at 3 and 12 weeks. Our approach is innovative because it seeks to address key issues in an understudied population using cutting edge methods. The proposed research is significant because it is expected to vertically advance the field by providing key insight into the important role of vaginal microbiota and exogenous hormones, which may lead to a new approach to HIV prevention among adolescent girls and young women.

2000 万新增性传播感染 (STI) 病例中有一半是年轻人（15-24 岁）感染在美国，每年有四分之一的性活跃少女患有性传播感染。复杂的生物、社会行为和文化因素使性活跃的青春期女孩感染性传播感染的风险更高与男孩和成年女性。一些性传播感染可以通过破坏保护性粘膜来增加艾滋病毒的感染率上皮屏障，促进炎症，并将 HIV 靶细胞招募到生殖道。这种协同作用性传播感染、炎症和艾滋病毒之间的关系导致青春期女孩中新增 38 万名艾滋病毒感染者每年全世界的年轻女性（10-24 岁）。在性传播感染和艾滋病毒流行率较高的社区，使用激素避孕 (HC) 但没有屏障保护的性活跃女孩面临感染性传播感染/艾滋病毒的风险获得。几项观察性研究表明，长效醋酸甲羟孕酮 (DMPA) 可能会使感染 HIV 的风险增加 3.0 倍。然而，性传播感染合并感染的生物学方面，青春期女孩和年轻女性的炎症、外源性激素和艾滋病毒感染待研究。鉴于大多数艾滋病毒感染发生在粘膜表面，迫切需要更好地了解粘膜免疫功能和生物因素，如激素状态和阴道微生物群，可以改变少女和年轻女性对性传播感染/艾滋病毒的易感性。在缺乏这些知识的情况下，开发有效的生物医学技术，以在这个脆弱的关键地区预防性传播感染和艾滋病毒人口可能仍然困难。我们的中心假设是 DMPA 诱导的低雌激素血症通过改变微生物群（例如，减少乳酸菌），降低粘液病原体捕获特性，并增加炎症。测试根据我们的假设，我们提出以下两个具体目标：（1）确定阴道微生物群、炎症和性传播感染。 225 名月经初潮、性活跃、健康的美国女性的阴道微生物群青春期女孩和年轻女性（13-24岁）将通过使用自我测序的16s rRNA测序来表征以横截面设计收集阴道拭子； (2) 确定 DMPA 使用对阴道的影响微生物群、炎症和女性生殖道解剖学和生理学。青春期女孩的一个子集和开始使用 DMPA 的年轻女性 (n=40) 或不使用任何 HC 的年轻女性 (n=40) 将进行前瞻性随访。阴道微生物群、炎症和宫颈阴道粘液特性相对于基线的变化将是在第 3 周和第 12 周进行评估。我们的方法是创新的，因为它寻求解决关键问题使用尖端方法对未充分研究的人群进行研究。拟议的研究意义重大，因为它预计通过提供对阴道微生物群重要作用的关键见解来垂直推进该领域和外源性激素，这可能会导致在青春期女孩和女性中预防艾滋病毒的新方法年轻女性。