Systemic and mucosal immune dysregulation and HIV risk in transgender females

跨性别女性的全身和粘膜免疫失调和艾滋病毒风险

• 批准号: 9927104
• 负责人: Mimi Ghosh
• 金额: $ 20.06万
• 依托单位: GEORGE WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-12-20 至 2021-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9927104
• 关键词: AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Address; Affect; Age; Anal Sex; Androgens; Animal Model; Behavioral; Biological; Biological Response Modifiers; Blood; Chronic; Clinical Research; Communities; Data; District of Columbia; Dose; Epidemic; Estradiol; Estrogens; Exposure to; Female; Funding; Gender; Goals; HIV; HIV Infections; HIV risk; Health; Immune; Immune response; Immune system; Impairment; In Vitro; Inflammation; Inflammation Mediators; Inflammatory; Institutes; Intervention; Knowledge; Lead; Life; Link; Long-Term Effects; Medical; Mental Depression; Mucous Membrane; Participant; Pathway interactions; Periodicity; Peripheral Blood Mononuclear Cell; Phenotype; Plasma; Population; Predisposition; Production; Recommendation; Reporting; Research; Research Design; Research Personnel; Risk; Risk Assessment; Sexual Health; Sexual and Gender Minorities; Stress; Swab; United States National Institutes of Health; Violence; Vulnerable Populations; Walkers; cis-female; cis-male; cohort; cytokine; design; dosage; dysbiosis; female sex hormone; follow-up; gender nonconforming; high risk; hormone therapy; hypothalamic-pituitary-adrenal axis; immune function; in vivo; interest; male; men; men who have sex with men; microbiome; negative affect; recruit; rectal; rectal microbiome; response; sex; social; social stigma; stressor; transgender; tumor-immune system interactions; xenoestrogen

Project Summary/Abstract: Trans-females who have sex with men (TFSM) and men are a population disproportionately affected by the HV/AIDS epidemic. Although often grouped together with cis-men who have sex with men (MSM) due to the practice of receptive anal intercourse, TFSM have a unique immune phenotype due to life-long exposure to female sex hormones such as estradiol (E2). As E2 can modulate multiple systemic and mucosal immune parameters, it is critical to determine whether long-term synthetic estrogen exposure in those who are genetically male, adversely impact HIV susceptibility. Currently, there is a gap in the knowledge as to the extent to which long-term synthetic E2 therapy affects systemic immune responsiveness, and rectal mucosal immune microenvironment including the microbiome, in the context of HIV infection. The goal of this proposal is to identify dysregulation in systemic and mucosal immune pathways that are relevant to the risks of acquiring HIV. We will evaluate HIV uninfected TFSM who are starting gender- affirming hormone therapy (GAHT) and follow them up after 3 months (cohort 1), as well as those who have been on GAHT for at least 1 year (cohort 2). This study design allows us to compare immune condition and function in TFSM without E2 therapy, with short-term E2 therapy and with long-term E2 therapy. We have unique access to this population through Dr. Goldstein, the Director of Clinical Research at Whitman Walker Institute, Washington DC, who is actively involved in transgender health research and a co-investigator on this proposal. We propose to recruit 30-40 participants per group and collect blood for analysis of systemic immune responses and rectal swabs for analysis of mucosal immune microenvironment and microbiome. There is a growing interest in the National Institutes of Health (NIH) toward funding transgender research. However, data is severely lacking in our understanding of immuno-biological mechanisms that may affect HIV acquisition in TFSM. Further, this proposal is responsive to the recently issued NOSI, NOT-MD-19-001 (Research on the Health of Sexual and Gender Minority (SGM) Populations). Assessment of data obtained from this study will spur further research that may alert the scientific and medical community of unexplored risks and lead to well-informed recommendations and interventions.

项目摘要/摘要： 变性女性与男性发生性关系(TFSM)和男性是受 HV/艾滋病流行。虽然经常与顺位男男性行为者(MSM)组合在一起，但由于 接受性肛交的实践，由于终生接触女性，TFSM具有独特的免疫表型 性激素，如雌二醇(E2)。由于雌二醇可以调节多种系统和粘膜免疫参数，所以它 对确定基因男性长期接触合成雌激素是否会对 影响艾滋病毒易感性。 目前，对于长期的合成雌二醇组治疗对全身的影响程度还存在认识上的差距。 免疫反应性和直肠粘膜免疫微环境，包括微生物组 艾滋病毒感染的可能性。这项建议的目标是确定全身和粘膜免疫途径的失调。 这与感染艾滋病毒的风险有关。我们将评估那些开始性行为的未感染艾滋病毒的TFSM- 肯定激素治疗(GAHT)并在3个月后随访(队列1)，以及那些已经接受过激素治疗的人 服用GAHT至少1年(队列2)。这项研究设计使我们能够比较免疫状况和功能在 TFSM不接受E2治疗，短期接受E2治疗，长期接受E2治疗。 我们通过惠特曼临床研究总监戈尔茨坦博士获得了接触这一人群的独特途径 沃克研究所，华盛顿特区，积极参与变性人健康研究，也是 这项提议。我们建议每组招募30-40名参与者，并采集血液进行系统免疫分析 反应和直肠拭子用于粘膜免疫微环境和微生物群分析。 美国国立卫生研究院(NIH)对资助变性人研究的兴趣越来越大。然而， 我们对可能影响艾滋病病毒感染的免疫生物学机制的了解严重缺乏数据 TFSM。此外，该建议响应了最近发布的NOSI，NOT-MD-19-001(关于健康的研究 性少数群体和性别少数群体(SGM)。 对从这项研究中获得的数据的评估将刺激进一步的研究，这可能会提醒科学和医学 这是一项关于尚未探索的风险的社区，并导致知情的建议和干预措施。