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

– 炎症、阴道微生物群和 STI/HIV 风险 –

• 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
• 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

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.

年轻人（15-24岁）感染了2 000万新的性传播感染（STI） 在美国，每4个性活跃的少女中就有1人患有性传播感染。复杂的生理，社会- 行为和文化因素使性活跃的青春期女孩患性病的风险更高， 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。 上皮屏障，促进炎症，并招募HIV靶细胞进入生殖道。这种协同作用 性传播感染、炎症和艾滋病毒之间的相互作用导致了38万名少女新感染艾滋病毒 和年轻女性（10- 24岁）。在性传播感染和艾滋病毒流行率高的社区， 使用激素避孕（HC）但没有屏障保护的性活跃女孩有感染性传播感染/艾滋病毒的风险 采集一些观察性研究表明，长效醋酸甲羟孕酮（DMPA） 可能会增加艾滋病毒感染的风险高达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， 替补演员鉴于大多数艾滋病毒感染发生在粘膜表面，因此迫切需要更好地 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， 改变少女和年轻妇女对性传播感染/艾滋病毒的易感性。在缺乏这种知识的情况下， 发展有效的生物医学技术，在这一脆弱的关键领域预防性传播感染和艾滋病毒， 人口增长可能仍然困难。我们的中心假设是DMPA引起的低雌激素血症 通过改变微生物群（例如， 减少乳杆菌）、降低粘液病原体捕获性能并增加炎症。测试 我们的假设，我们提出了以下两个具体目标：（1）确定阴道之间的关联 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16 s rRNA测序进行表征， 在横断面设计中收集阴道拭子;（2）确定DMPA使用对阴道分泌物的影响。 微生物群、炎症和女性生殖道解剖学和生理学。一部分青春期女孩， 将前瞻性随访开始使用DMPA的年轻女性（n=40）或未使用任何HC的年轻女性（n=40）。 将评估阴道微生物群、炎症和宫颈阴道粘液性质相对于基线的变化。 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， 使用最先进的方法对未被充分研究的人群进行研究。这项研究之所以重要，是因为 预计将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 和外源激素，这可能会导致一种新的方法来预防青春期女孩的艾滋病毒， 年轻女性。