Cardiometabolic Effects of Gender-Affirming Hormonal Therapy among Transgender Women with HIV

项目摘要/摘要 在美国，大约三分之一的变性人携带艾滋病毒。艾滋病病毒携带者服用抗艾滋病药物 逆转录病毒治疗面临心脏代谢性疾病的风险增加，即使在控制了传统风险之后也是如此 各种因素。性别肯定激素疗法反过来可能会对变性人的代谢健康产生不利影响。 增加内脏脂肪组织，还可能增加心肌梗死和 静脉血栓栓塞症。威尔斯亲王患心脏代谢性疾病的风险增加 性别肯定激素治疗对未感染艾滋病毒的变性人妇女的已知效果强调 这项提案的目标的意义。 这项提议的中心假设是，在变性人WHIV中进行性别肯定激素治疗将 既有有益的心脏代谢影响，也有不利的心脏代谢影响，反映了 随之而来的是睾丸激素抑制和雌激素替代。应聘者将应用一种极具创新性的 首次前瞻性研究睾酮抑制和雌激素的作用 治疗：目标1-身体成分、异位脂肪沉积、胰岛素敏感性和血脂水平，目标2- 心肌结构和功能；目标3-凝血参数(包括凝血因子和组织 单核细胞上的因子表达)。这项提案将提供有关安全的迫切需要的信息 性别肯定疗法在这一人群中的应用，并确定激素辅助疗法的可能靶点 可优化变性人WHIV心脏代谢健康的治疗。 候选人是一位杰出的临床研究员，她致力于发展自己的研究轨道。 中心是艾滋病毒携带者变性人的心脏代谢健康。短期内，她希望 获得必要的技能，独立从事以病人为中心的生理学研究 艾滋病毒中的变性人医学和RO1提案的初步数据。从长远来看，她计划 利用这些技能和初步数据成为R01资助的临床研究人员。这项提案将是 由优秀的导师和合作者团队提供支持，他们将在以下方面提供互补的专业知识 艾滋病毒相关心脏代谢性疾病、心脏病学、传染病、免疫学和 生物统计学。麻省总医院和哈佛附属医院的制度环境 院校将为考生提供出色的资源和机会，使其能够顺利完成 提出的学习和职业发展计划。 。

PROJECT SUMMARY/ ABSTRACT Around one third of transgender individuals in the United States are living with HIV. People with HIV on anti- retroviral therapy face an increased risk of cardiometabolic disease, even after controlling for traditional risk factors. Gender-affirming hormone therapy, in turn, may adversely affect the metabolic health of transgender women by increasing visceral adipose tissue and may also increase the risk of myocardial infarctions and venous thromboembolism. The increased risk for cardiometabolic disease among PWH together with the known effects of gender-affirming hormone therapy among non-HIV-infected transgender women underscores the significance of the aims of this proposal. The central hypothesis for this proposal is that gender-affirming hormone therapy in transgender WHIV will have both beneficial and adverse cardiometabolic effects, reflecting complex downstream consequences of concomitant testosterone suppression and estrogen replacement. The candidate will apply a highly innovative approach to, for the first time, prospectively investigate the effect of testosterone suppression and estrogen therapy on: aim 1 - body composition, ectopic fat deposition, insulin sensitivity, and lipid levels, aim 2 – myocardial structure and function; aim 3 – coagulation parameters (including coagulation factors and tissue factor expression on monocytes). This proposal will provide critically needed information regarding the safety of gender-affirming therapy in this population and identify possible targets for adjunctive therapies to hormone therapy which may optimize the cardiometabolic health of transgender WHIV. The candidate is an outstanding clinical investigator who is dedicated to developing her own research track centered on the cardiometabolic health of transgender individuals living with HIV. In the short term, she hopes to obtain the necessary skills to independently pursue patient-oriented physiology research in the field of transgender medicine in HIV and the preliminary data for an RO1 proposal. In the long term, she plans to utilize these skills and preliminary data to become an R01-funded clinical investigator. This proposal will be supported by an excellent team of mentors and collaborators who will provide complementary expertise in the areas of HIV-associated cardiometabolic disease, Cardiology, Infectious Disease, Immunology and Biostatistics. The institutional environment of Massachusetts General Hospital (MGH) and Harvard-affiliated institutions will provide the candidate excellent resources and opportunities for successful completion of the proposed study and her career development plan. .