Sexual trauma and HIV susceptibility among women: the role of stress and genital immunity

女性性创伤和艾滋病毒易感性：压力和生殖器免疫力的作用

• 批准号: 9245577
• 负责人: Mimi Ghosh
• 金额: $ 55.52万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-20 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9245577
• 关键词: Adaptive Immune System; Address; Adolescent; Adult; Adverse effects; Affect; Age; Alcohol or Other Drugs use; Anal Sex; Biological; Biological Response Modifiers; Case-Control Studies; Cervical; Chronic; Clinic; Clinical assessments; Collaborations; Corticotropin; Data; Development; Discipline of obstetrics; Environment; Epithelial; Epithelium; Event; Female; Female Adolescents; Forcible intercourse; Fright; Future; Genital injury; Genital system; Goals; Gynecology; HIV; HIV Infections; HIV risk; Health; Hydrocortisone; IL8 gene; Immunity; Immunologic Factors; Immunologic Markers; Immunologics; Inflammation; Inflammation Mediators; Injury; Interleukin-1 alpha; Interleukin-1 beta; Interleukin-6; Investigation; Knowledge; Laboratories; Link; Local Microbicides; Measures; Mediation; Mediator of activation protein; Menstruation; Mental Health; Mucous Membrane; PI3 gene; Participant; Pathway interactions; Peripheral; Pharmaceutical Preparations; Plasma; Play; Population; Predisposition; Prevention strategy; Recruitment Activity; Research; Risk; Risk Behaviors; Risk Factors; Role; SLPI gene; Salivary; Sex Functioning; Stress; Surveys; TNF gene; Time; Trauma; United States National Institutes of Health; Vagina; Violence; Visit; Woman; Women' s Role; aged; base; beta-Defensins; cervicovaginal; community center; condoms; dehydroepiandrosterone; epidemiologic data; experience; follow-up; functional loss; genital secretion; girls; high risk behavior; hormone therapy; hypothalamic-pituitary-adrenal axis; immune activation; immune function; male; multidisciplinary; novel strategies; pre-exposure prophylaxis; reproductive; reproductive tract; research and development; sex; sex risk; sexual trauma; sexual violence; transmission process; traumatic event

Project Summary Extensive epidemiological data has documented an association between sexual violence and HIV acquisition through direct and indirect pathways. However, the underlying biological mechanism to explain this association is less understood. Sexual violence may contribute to HIV acquisition by disrupting the cervicovaginal epithelium and magnifying local inflammation and immune activation. Sexual violence may also alter the hypothalamic-pituitary-adrenal (HPA) axis resulting in changes to the innate and adaptive immune system in the female genital tract (FGT) and alterations to cervicovaginal epithelial health. When compared to adult women, adolescent girls may be at heightened biological risk due to differences in the genital mucosa such as cervical ectopy and high baseline inflammation rendering girls more vulnerable to adverse effects of stress. Our preliminary data indicate both recent and chronic cases of sexual violence cause dysregulation of critical FGT immune mediators that have the potential to affect HIV susceptibility. Establishing a better understanding of the correlation between immunity in the FGT and the dysregulated HPA axis, as well as the differences between adolescent girls and adult women is critical for the development of strategies to counter the adverse effects of sexual trauma resulting from mucosal injury in efforts to reduce the risk of HIV acquisition. To that end, we will: 1) assess the impact of sexual trauma on FGT immunity; 2) assess the impact of sexual trauma on the central and peripheral HPA axis; 3) determine the extent to which the dysregulated HPA axis affects FGT immunity following sexual trauma; and 4) examine whether risk factors linked to sexual violence (i.e., sexual risk behaviors, substance use, mental health) are associated with HPA axis dysregulation and FGT immunity in adolescent girls and adult women post-sexual trauma. We will further determine how these associations change over time following the traumatic event. Our multi-disciplinary team will conduct a case- control study with follow-up among adolescent girls aged 14-19 n=30; 15 cases and 15 controls) and adult women aged 20 and older (n=30; 15 cases and 15 controls). All participants will complete a quantitative survey and clinical assessment at baseline, 1- and 3-month follow-up visits. The proposed research will advance the FY2016 Trans-NIH Plan for HIV-related Research by “examining the relationship of the female genital tract immune function, including genital injury due to sexual violence, to HIV risk” and is highly responsive to RFA- AI-15-058 by “conducting research that addresses the gaps in our understanding of how reproductive maturation impacts HIV susceptibility.” Findings from this research will facilitate future hypothesis-driven longitudinal research and development of safe and efficacious biomedical prevention strategies.

项目概要 大量流行病学数据记录了性暴力与艾滋病毒感染之间的关联 通过直接和间接途径。然而，解释这种关联的潜在生物学机制 较少被理解。性暴力可能会破坏宫颈阴道功能，从而导致艾滋病毒感染 上皮细胞并放大局部炎症和免疫激活。性暴力也可能改变 下丘脑-垂体-肾上腺（HPA）轴导致先天性和适应性免疫系统的变化 女性生殖道（FGT）和宫颈阴道上皮健康的改变。与成人相比 由于生殖器粘膜的差异，妇女和少女可能面临更高的生物学风险，例如 宫颈异位和高基线炎症使女孩更容易受到压力的不利影响。 我们的初步数据表明，近期和长期发生的性暴力案件都会导致关键性的失调。 FGT 免疫介质有可能影响 HIV 易感性。建立更好的理解 FGT 免疫与 HPA 轴失调之间的相关性以及差异 少女和成年妇女之间的差距对于制定应对不利影响的战略至关重要 粘膜损伤引起的性创伤的影响，以努力降低感染艾滋病毒的风险。对此 最后，我们将：1）评估性创伤对FGT免疫力的影响； 2）评估性创伤的影响 在中央和外围 HPA 轴上； 3) 确定HPA轴失调的影响程度 性创伤后的 FGT 免疫力； 4) 检查是否存在与性暴力相关的风险因素（即 性危险行为、药物滥用、心理健康）与 HPA 轴失调和 FGT 相关 青春期女孩和成年女性在性创伤后的免疫力。我们将进一步确定如何这些 创伤事件发生后，关联会随着时间的推移而发生变化。我们的多学科团队将进行案例- 对照研究，对 14-19 岁少女进行随访，n=30； 15 例病例和 15 例对照）和成人 20 岁及以上女性（n=30；15 例病例和 15 例对照）。所有参与者将完成定量调查 以及基线、1 个月和 3 个月随访时的临床评估。拟议的研究将推进 2016 财年跨 NIH 艾滋病毒相关研究计划“检查女性生殖道的关系” 免疫功能，包括性暴力造成的生殖器损伤，艾滋病毒风险”，并且对 RFA 高度敏感 AI-15-058 通过“开展研究来解决我们对生殖如何理解的差距” 成熟会影响艾滋病毒的易感性。”这项研究的结果将有助于未来的假设驱动 纵向研究和开发安全有效的生物医学预防策略。