Understanding the rectal mucosal effects of cross-sex hormone therapy among US and Thai transgender women

了解跨性别激素治疗对美国和泰国变性女性直肠粘膜的影响

• 批准号: 10227723
• 负责人: Colleen F Kelley
• 金额: $ 68.82万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10227723
• 关键词: AIDS prevention; AIDS/HIV problem; Anal Sex; Animals; Attention; Bacteroidaceae; Biological; Biology of HIV Transmission; Biopsy; CD4 Positive T Lymphocytes; Cells; Centers for Disease Control and Prevention (U.S.); Clinical Research; Clinical Trials; Clinical Trials Unit; Cross-Sectional Studies; Development; Enrollment; Epithelial Cells; Estrogen Receptor beta; Estrogen Therapy; Estrogens; Exogenous Hormone Therapy; Exposure to; Female genitalia; Flow Cytometry; Future; Gene Expression Profile; General Population; Goals; Gonadal Steroid Hormones; HIV; HIV Infections; HIV Seronegativity; HIV prevention trial; HIV vaccine; Hormones; Immune; Immunohistochemistry; Immunologics; Immunology; Infection; Inflammatory; Infrastructure; International; Intervention; Intestinal Mucosa; Knowledge; Longitudinal cohort; Modeling; Mucositis; Mucous Membrane; Phenotype; Physiological; Pilot Projects; Population; Population Biology; Predisposition; Prevalence; Prevention; Prevention Research; Progesterone; Rectum; Reporting; Research; Risk; Sampling; Site; Structure; Thailand; Time; Vaccines; Work; base; cis-male; cohort; design; efficacy evaluation; experimental study; high risk men; hormone therapy; human model; immune activation; improved; inflammatory marker; men who have sex with men; microbiome; microbiota; mucosal microbiota; next generation sequencing; preventive intervention; programs; psychosocial; receptor expression; rectal; rectal HIV transmission; reproductive tract; transcriptome; transcriptome sequencing; transgender; transgender women; transgender women who have sex with men; transmission process; virtual

PROJECT SUMMARY Until recently, the specific HIV prevention needs of transgender populations received insufficient attention, and the biology of HIV transmission, specifically, has been understudied to date. Transgender women who have sex with men (TGWSM) are at elevated risk for HIV acquisition with global HIV prevalence rates approximately 20% and odds of infection 48 times the general population. Engaging in condomless receptive anal intercourse (CRAI) is common among TGWSM, and the physiologic efficiency of HIV transmission across the rectal mucosa facilitates HIV transmission. Historically, TGWSM have been grouped with men who have sex with men (MSM) in HIV prevention studies due to presumed similar risks of rectal HIV exposure despite their unique psychosocial, biologic, and prevention needs. From a biologic perspective, many TGWSM use cross-sex hormone therapy with uncertain rectal mucosal effects. The effects of endogenous and exogenous hormones in the human and animal-model female genital tract has been described with estrogen generally being seen as hindering HIV transmission and progesterone facilitating transmission; however, few studies report effects on the rectal mucosa. In addition, the intestinal mucosa is known to be steroidogenic, and colonic epithelial cells express estrogen receptor β, suggesting that exogenous hormone therapy likely has an effect on the rectal mucosa that could influence HIV transmission. In this application, we will build upon our successful translational mucosal immunology program with a highly successful clinical research and retention infrastructure that was designed to understand factors that may influence rectal HIV transmission and propose to examine the effects of cross-sex hormone therapy on the rectal mucosal resident cellular populations, transcriptome, and microbiome in TGWSM. In addition, we will capitalize on the existing infrastructure of the Emory/CDC HIV/AIDS Clinical Trials Unit and expand our studies to an international site, Bangkok, in order to make global comparisons in our findings. In aim 1, we will compare HIV target cell availability in 1) TGWSM on estrogen therapy, 2) TGWSM on estrogen + progesterone therapy, and 3) cisgender MSM. We will also examine HIV target cell availability in TGWSM before and after initiating cross-sex hormone therapy in a longitudinal cohort. In aim 2, we will compare the transcriptome by RNA-seq between groups in the cross- sectional cohort and before and after initiating cross-sex hormone therapy in the longitudinal cohort in order to identify new targets for biomedical HIV prevention interventions. Finally, in aim 3, we will define the differences in the rectal mucosal microbiota associated with cross-sex hormone therapy in order to inform the design of future HIV prevention intervention clinical trials. The overarching goal of this proposal is to achieve a better understanding of the rectal mucosal effects of cross-sex hormones that will allow for the optimization of current biomedical HIV prevention interventions and enhance design of future interventions, including an effective vaccine, for TGWSM. !

项目摘要 直到最近，接收到的跨性别受欢迎的特定艾滋病毒预防需求， 迄今为止，艾滋病毒传播的生物学已被了解。 与男性的性行为（TGWSM）的艾滋病毒感染风险较高 20％和感染的几率是普通人群的48倍。 （CRAI）在TGWSM中很常见，并且直肠跨度HIV的生理功效 粘膜促进了艾滋病毒的传播。 艾滋病毒中的男性（MSM）由于录制的类似风险而归因于艾滋病毒 从生物学的角度来看，心理社会，生物学和预防需求。 荷尔蒙治疗不确定的记录作用。 在人类和动物模型中，女性生殖道被描述为雌激素，通常被视为 阻碍艾滋病毒传播和孕激素促进传播； 记录。此外，已知肠粘膜是类固醇的 表达雌激素受体β，表明Thormone治疗可能对直肠有影响 可能影响艾滋病毒传播的粘膜。 具有非常成功的临床研究和退化的翻译粘膜免疫学计划 旨在了解可能影响直肠艾滋病毒传播的因素并提出的基础设施 为了检查跨性别激素治疗对记录驻留细胞种群的影响， 转录组和TGWSM中的微生物组。 Emory/CDC HIV/AIDS临床试验单元，并将我们的研究扩展到曼谷的国际网站，以便 在AIM 1中进行全球比较。 雌激素治疗，2）TGWSM在雌激素 +孕酮治疗上，3）我们也将 在A之前检查TGWSM中的HIV靶细胞可利用性，并在A中反应跨性激素治疗 纵向队列。 分段队列以及在纵向队列中启动跨性别激素治疗之前和之后 确定生物医学艾滋病毒预防的新目标。 在与跨性别激素疗法相关的疾病中 未来的Hivevention临床试验。 了解跨性激素的沉积作用，这将允许优化电流的电流 生物医学艾滋病毒预防介入国际和增强未来干预措施的设计，包括有效的 疫苗，用于TGWSM。 呢