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.

项目摘要 广泛的流行病学数据已经记录了性暴力与艾滋病毒收购之间的关联 通过直接和间接的途径。但是，解释这种关联的基本生物学机制 不了解。性暴力可能会通过破坏子宫颈阴道来导致艾滋病毒的获取 上皮和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，导致对先天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 妇女，由于生殖器粘膜的差异，例如 宫颈肾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最近和慢性性暴力案件导致关键的失调 FGT免疫介质具有影响HIV敏感性的潜力。建立更好的理解 FGT中免疫力与失调的HPA轴以及差异之间的相关性 青春期女孩和成年女性之间对于制定反对不利的策略至关重要 粘膜损伤引起的性创伤的影响，以减少艾滋病毒收购风险。为此 最后，我们将：1）评估性创伤对FGT免疫的影响； 2）评估性创伤的影响 在中央和外围HPA轴上； 3）确定HPA轴失调的程度 性创伤后FGT免疫力； 4）检查是否与性暴力有关的风险因素是否与性暴力有关（即 性风险行为，药物使用，心理健康）与HPA轴失调和FGT有关 青春期女孩和成年妇女的免疫力在性交后创伤。我们将进一步确定这些 创伤事件之后的关联随时间变化。我们的多学科团队将进行案件 - 对照研究与14-19岁n = 30岁的青少年女孩的随访； 15例和15个对照）和成人 20岁及20岁以上的妇女（n = 30; 15例和15例对照）。所有参与者将完成定量调查 以及基线时的临床评估，1个月和3个月的随访访问。拟议的研究将推动 2016财年，通过检查女性生殖道的关系，用于HIV相关研究的Trans-NIH计划 免疫功能，包括因性暴力引起的生殖器损伤，艾滋病毒风险”，对RFA的反应很高 AI-15-058通过“进行研究，以解决我们对生殖方式的理解中的差距 成熟影响艾滋病毒的敏感性。”这项研究的发现将有助于未来的假设驱动 安全有效的生物医学预防策略的纵向研究和开发。