Mechanisms underlying recurrent bacterial vaginosis and HIV risk A Multidisciplinary approach

复发性细菌性阴道病和艾滋病毒风险的机制 多学科方法

• 批准号: 10219065
• 负责人: MARIA LUISA ALCAIDE
• 金额: $ 72.87万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-20 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10219065
• 关键词: 16S ribosomal RNA sequencing; AIDS prevention; Address; Affect; Age; Anti-Retroviral Agents; Antibiotic Therapy; Antibiotics; Automobile Driving; Bacteria; Bacterial Vaginosis; Bacteriophages; Behavioral; Biological Factors; Cells; Cities; Coculture Techniques; Communities; DNA sequencing; Development; Drug usage; Environment; Epithelial; Female; Flow Cytometry; Genetic; Gram-Negative Anaerobic Bacteria; HIV; HIV Infections; HIV risk; Health; Hygiene; Immune; Immune response; Immunity; Immunologics; Impairment; In Vitro; Incidence; Inflammation; Inflammatory; Inflammatory Response; Intervention; Irrigation; Knowledge; Lead; Longitudinal Studies; Maintenance; Mass Spectrum Analysis; Measures; Metabolism; Metronidazole; Microbiology; Mucosal Immune Responses; Mutation; Pharmaceutical Preparations; Questionnaires; Race; Recurrence; Regulation; Risk; Role; Self Administration; Sex Behavior; Sexually Transmitted Diseases; Shotguns; Technology; Treatment Efficacy; Treatment Failure; United States National Institutes of Health; Vagina; Vaginal Douching; Viral; Woman; bacterial community; bacterial metabolism; base; cervicovaginal; cohort; cytokine; drug metabolism; effective therapy; genital infection; in vivo; ineffective therapies; interdisciplinary approach; intraepithelial; microbial; microbial community; microbiome; microbiota; prevent; reproductive; reproductive tract; sociodemographic factors; transcription factor; transcriptome sequencing; vaginal lactobacilli; vaginal microbiome; vaginal microbiota; virome

Abstract Bacterial vaginosis (BV), the most common health condition affecting the female reproductive tract, significantly increases the risk of HIV and STI acquisition in women. BV is characterized by changes in the composition of the vaginal bacteria (microbiota), with a reduction in healthy vaginal Lactobacillus species and an increase in gram negative anaerobic bacteria. Women with BV have impaired female reproductive tract mucosal immune responses with increased HIV target cells, as well as decreased epithelial integrity; all which lead to increased HIV risk. Furthermore, a recent study demonstrated that BV-associated bacteria can directly hydrolyze drugs used for HIV prevention, setting up conditions that undermine treatment efficacy. Current antibiotic-based treatments for BV result in failure of treatment or recurrence in the majority of women. Behavioral (sexual behaviors and intravaginal hygiene practices such as intravaginal douching), bacterial factors (microbiome and virome), and host biological factors (mucosal immune responses and inflammation), all may underscore BV recurrence. In this study, we will assess the mechanisms underlying BV recurrence in a unique cohort of reproductive age women (18-45 years) with BV. Reproductive age women with BV will be provided BV treatment and followed longitudinally (one and six months post-BV treatment). Study aims are: 1) To evaluate the role of intravaginal hygiene practices on BV recurrence; 2) To evaluate the role of the vaginal microbiome and virome, and antibiotic metabolism by vaginal bacteria, on BV recurrence; and 3) To evaluate the role of host biological factors on BV recurrence. To our knowledge, this is the first study to mechanistically assess factors that underlie BV recurrence in vivo in a longitudinal study, and specifically, using a comprehensive, multidisciplinary approach (behavioral, microbiological, and immunological). We will use cutting edge technologies to measure these potential mechanisms relative to BV recurrence. Study results will be critical to develop targeted intervention strategies to prevent BV recurrence and thus, better protect women from HIV and STIs.

摘要 细菌性阴道病（BV）是影响女性生殖道的最常见健康状况， 这大大增加了妇女感染艾滋病毒和性传播感染的风险。BV的特征是 阴道细菌（微生物群）的组成，减少健康的阴道乳杆菌属物种， 革兰氏阴性厌氧菌的增加。BV女性生殖道受损 粘膜免疫反应与HIV靶细胞增加，以及上皮完整性降低;所有这些 导致艾滋病风险增加。此外，最近的一项研究表明，BV相关细菌可以直接 水解用于预防艾滋病毒的药物，造成损害治疗效果的条件。电流 BV的药物治疗导致大多数女性治疗失败或复发。 行为（性行为和阴道内卫生习惯，如阴道内冲洗），细菌 因子（微生物组和病毒组）和宿主生物因子（粘膜免疫应答和炎症）， 所有这些都可能强调BV复发。在这项研究中，我们将评估BV复发的潜在机制， 生殖年龄女性（18-45岁）BV患者的独特队列。患有BV的育龄女性将被 提供BV治疗并纵向随访（BV治疗后1个月和6个月）。研究目的：1） 评估阴道内卫生习惯对BV复发的作用; 2）评估阴道内卫生习惯对BV复发的作用。 微生物组和病毒组以及阴道细菌的抗生素代谢对BV复发的影响;以及3）评估 宿主生物学因素在BV复发中的作用。据我们所知，这是第一个研究， 在纵向研究中评估体内BV复发的基础因素，特别是使用 全面的多学科方法（行为学、微生物学和免疫学）。我们将使用 尖端技术来测量这些与BV复发相关的潜在机制。研究结果将 制定有针对性的干预策略以预防BV复发至关重要，从而更好地保护妇女 艾滋病和性传播感染