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: 10257722
• 负责人: Theresa L Chang
• 金额: $ 19.58万
• 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 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10257722
• 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; 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 跨性别者比奇特德人更高的艾滋病毒收购风险。变性青年更多 可能比异性恋年轻人报告性活动的早期发作，有更多的性伴侣，并且 在上次性交中使用避孕套的可能性较小，从而使他们面临收购艾滋病毒的风险。 尽管行为和社会心理因素会导致跨性别者的艾滋病毒风险较高，但性别肯定 激素（GAH）治疗（即，出生时分配女性的跨性别者睾丸激素（AFAB）或 分配男性在出生时分配男性（AMAB）的雌激素/抗雄激素（AMAB）可能会改变生物学因素， 导致HIV传播增加。我们的目标是确定与 跨性别者的艾滋病毒风险增加，以预防艾滋病毒的长期目标。性激素是已知的 调节免疫反应，导致宿主对病原体的敏感性变化，疫苗功效 和药物代谢。知识的关键差距是GAH治疗的免疫学后果 跨性别人群仍然未知。我们已经表明，荷尔蒙避孕药给药改变了 HIV偏好的免疫标记，并增加CD4+ T细胞对女性HIV的敏感性。性别 激素还改变了粘膜免疫环境，阴道微生物组，离体HIV感染性和体外HIV 原代细胞的感染。我们最近发现，年轻人（18-25岁）患有较高的HIV风险免疫 与成人受试者（27-41岁）相比，离体HIV感染谱。因此，变性青年可能在 由于年龄和GAH（雌激素/抗雄激素或睾丸激素）介导的免疫属性引起的特殊风险 偏爱艾滋病毒感染。我们的目的是确定GAH治疗对免疫调节和 确定与年轻跨性别人群中HIV敏感性增加有关的免疫属性。我们 假设GAH治疗会改变影响跨性别青年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内HIV 基线时AFAB和AMAB个体的感染以及1、3和6个月的GAH治疗，低至 高浓度激素。鉴于最近的发现，抗返回病毒疗法在 跨性别妇女，我们的结果将为正在接受的个人提供更好的治疗 激素疗法和更有效的HIV预防策略的设计。