Impact of gender affirming hormone therapy on immune modulation and HIV infection in transgender young adults

性别肯定激素治疗对跨性别年轻人免疫调节和艾滋病毒感染的影响

• 批准号: 10364706
• 负责人: Theresa L Chang
• 金额: $ 23.55万
• 依托单位: RBHS-NEW JERSEY MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-04 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10364706
• 关键词: AIDS prevention; Accounting; Adolescent and Young Adult; Adult; Age; Androgen Antagonists; Area; Automobile Driving; Behavioral; Biological Factors; Biological Response Modifiers; Birth; Blood; CCR5 gene; CD4 Positive T Lymphocytes; Cells; Cervical; Contraceptive Agents; Dendritic Cells; Depo Provera; Development; Diagnosis; Disease; Estrogens; Female; Frequencies; Gender; Goals; Gonadal Steroid Hormones; HIV; HIV Infections; HIV diagnosis; HIV risk; Heterosexuals; Hormones; Immune; Immune response; Immunologic Factors; Immunologic Markers; Immunologics; Immunotherapy; In Vitro; Individual; Interleukin-1 beta; Interleukin-17; Knowledge; Lead; Light; Longitudinal Studies; Mediating; Mucosal Immune Responses; Mucous Membrane; Pathway interactions; Peripheral; Peripheral Blood Mononuclear Cell; Persons; Phenotype; Population; Predisposition; Prevention strategy; Primary Infection; Production; Progesterone; Psychosocial Factor; Reporting; Research; Risk; Sampling; Sex Behavior; Sexual Partners; Sexually Transmitted Diseases; T-Lymphocyte; TNF gene; Testosterone; Time; Vagina; Woman; Youth; aged; antiretroviral therapy; cell type; cervicovaginal; cisgender; clinically relevant; condoms; design; drug metabolism; early onset; gender dysphoria; high risk; hormonal contraception; hormone therapy; immune function; immunoregulation; inflammatory milieu; insight; integrin alpha4beta7; male; men; metabolome; microbiome; pathogen; preference; rectal; response; sex; single-cell RNA sequencing; therapy design; transgender; transgender women; transmission process; vaccine efficacy; vaccine response; vaginal microbiome; young adult

Project Summary Transgender people have a higher risk of HIV acquisition than cisgender people. Transgender youth are more likely than heterosexual youth to report early onset of sexual activity, have more lifetime sexual partners, and are less likely to use a condom with last intercourse placing them at an increased risk of acquiring HIV. Although behavioral and psychosocial factors lead to a higher HIV risk in transgender people, gender-affirming hormone (GAH) treatment (i.e., testosterone for transgender individuals assigned female at birth (AFAB) or estrogen/antiandrogen for transgender individuals assigned male at birth (AMAB)) may alter biological factors, resulting in increased transmission of HIV. Our goal is to determine immune attributes associated with increased HIV risk in transgender people, with the long-term goal of HIV prevention. Sex hormones are known to modulate the immune response, resulting in changes in host susceptibility to pathogens, vaccine efficacy and drug metabolism. A key gap in knowledge is that the immunological consequences of GAH therapy in transgender populations remains unknown. We have shown that hormonal contraceptive administration alters immune markers for HIV preference and increases susceptibility of CD4+ T cells to HIV in women. Sex hormones also alter the mucosal immune milieu, vaginal microbiome, ex vivo HIV infectivity, and in vitro HIV infection of primary cells. We recently discovered that young adults (aged 18-25) had higher HIV risk immune and ex vivo HIV infection profiles than adult subjects (aged 27-41). Thus, transgender youth may be at particular risk due to age- and GAH (estrogen/antiandrogen or testosterone)-mediated immune attributes that favor HIV infection. Our objective here is to determine the effect of GAH therapy on immune regulation and to identify immune attributes associated with increased HIV susceptibility in young transgender individuals. We hypothesize that GAH therapy alters immune functions that impact HIV infection in the transgender youth. We will conduct a longitudinal study to determine peripheral and mucosal immune responses and ex vivo HIV infection in AFAB and AMAB individuals at baseline and after 1, 3, and 6 months of GAH treatment with low to high concentrations of hormones. In light of recent findings that anti-retroviral therapies are less effective in transgender women, our results will inform both development of better treatments for individuals undergoing hormone therapy and the design of more effective HIV prevention strategies.

项目摘要 跨性别者比顺性别者感染艾滋病毒的风险更高。跨性别青年更多 比异性恋青年更可能报告性活动的早期发生，有更多的终身性伴侣， 在最后一次性交中不太可能使用避孕套，这增加了他们感染艾滋病毒的风险。 尽管行为和心理社会因素导致变性人感染艾滋病毒的风险更高， 激素（GAH）治疗（即，出生时分配为女性的跨性别个体的睾酮（AFAB），或 用于出生时指定为男性的变性个体的雌激素/抗雄激素（AMAB））可能改变生物学因素， 导致艾滋病毒传播增加。我们的目标是确定免疫属性与 跨性别者感染艾滋病毒的风险增加，长期目标是预防艾滋病毒。性激素是已知的 调节免疫应答，导致宿主对病原体的易感性、疫苗效力 和药物代谢。一个关键的知识缺口是GAH治疗的免疫学后果， 跨性别人口仍然未知。我们已经表明，激素避孕药的管理改变 HIV偏好的免疫标记物，并增加女性中CD 4 + T细胞对HIV的易感性。性 激素还改变粘膜免疫环境、阴道微生物组、离体HIV感染性和体外HIV 感染原代细胞。我们最近发现，年轻人（18-25岁）有较高的艾滋病毒风险免疫力， 和离体HIV感染谱。因此，跨性别青年可能在 由于年龄和GAH（雌激素/抗雄激素或睾酮）介导的免疫属性， 有利于艾滋病毒感染。我们的目的是确定GAH治疗对免疫调节的影响， 确定与年轻跨性别者艾滋病毒易感性增加相关的免疫属性。我们 假设GAH治疗改变了影响跨性别青年HIV感染的免疫功能。我们 将进行一项纵向研究，以确定外周和粘膜免疫反应和体外HIV AFAB和AMAB个体在基线和GAH治疗1、3和6个月后的感染， 高浓度的荷尔蒙。根据最近的研究结果，抗逆转录病毒疗法对 跨性别女性，我们的研究结果将告知两个发展更好的治疗个人经历 激素治疗和设计更有效的艾滋病毒预防战略。