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 变性人比顺性人感染艾滋病毒的风险更高。变性人青年更多 与异性恋青年相比，他们报告的性行为发生得更早，拥有更多的终身性伴侣 不太可能在最后一次性交时使用避孕套，这使他们感染艾滋病毒的风险增加。 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，但性别肯定 激素(GAH)治疗(即，对出生时为女性的变性人(AFAB)或 变性人出生时指定为男性(AMAB)的雌激素/抗雄激素)可能会改变生物因素， 导致艾滋病毒传播增加。我们的目标是确定与 增加变性人感染艾滋病毒的风险，长期目标是预防艾滋病毒。性激素是已知的 为了调节免疫反应，从而改变宿主对病原体的易感性，疫苗的效力 和药物新陈代谢。知识中的一个关键差距是GAH治疗的免疫学后果 变性人的人数仍然未知。我们已经证明，荷尔蒙避孕药可以改变 HIV偏好的免疫标记物和增加妇女的CD4+T细胞对HIV的易感性。性 激素也会改变粘膜免疫环境、阴道微生物群、体外HIV感染性和体外HIV 原代细胞感染。我们最近发现，年轻人(18-25岁)对艾滋病毒的免疫风险更高 与成人受试者(年龄27-41岁)相比，体外感染HIV的情况更明显。因此，变性人青年可能在 年龄和GAH(雌激素/抗雄激素或睾酮)介导的免疫属性导致的特殊风险 支持艾滋病病毒感染。我们的目标是确定GAH疗法的免疫调节作用，并 确定与年轻变性人艾滋病毒易感性增加相关的免疫属性。我们 假设GAH治疗改变了影响变性人青年艾滋病毒感染的免疫功能。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艾滋病毒 AFAB和AMAB患者在基线和GAH治疗1、3和6个月后感染情况 荷尔蒙浓度过高。鉴于最近的研究发现，抗逆转录病毒疗法在 对于变性女性，我们的结果将为两种更好的治疗方法的发展提供信息 荷尔蒙疗法和设计更有效的艾滋病毒预防战略。