Transgender Youth and PrEP: PK, Safety, Uptake & Adherence

跨性别青少年和 PrEP：PK、安全性、摄取

• 批准号: 10545355
• 负责人: Sybil Hosek
• 金额: $ 5.85万
• 依托单位: HEKTOEN INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-15 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10545355
• 关键词: AIDS prevention; AIDS/HIV problem; Address; Adherence; Adolescent; Adolescent and Young Adult; Affect; Age; Attention; Behavioral; Birth; Cognitive; Communities; Couples; Data; Data Reporting; Development; Developmental Process; Directly Observed Therapy; Drug Exposure; Drug Interactions; Drug Kinetics; Effectiveness; Environmental Risk Factor; Epidemic; Estradiol; Ethnography; FDA approved; Feedback; Female; Focus Groups; Fright; Fumarates; Gender; Gender Identity; Gonadal Steroid Hormones; HIV; HIV Infections; HIV prevention trial; Heterosexuals; Hormones; Incidence; Individual; Intervention; Interview; Kidney; Legal; Medical; Minerals; Modeling; Monitor; Motivation; Participant; Pharmaceutical Preparations; Phase; Physiologic calcification; Population; Prevalence; Process; Provider; Public Health; Randomized; Randomized Controlled Trials; Renal function; Research Project Grants; Risk; Safety; Sexual Development; Subgroup; Tenofovir; Testosterone; United States; Variant; Vulnerable Populations; Youth; appropriate dose; base; behavior change; biobehavior; bone; cohort; empowerment; emtricitabine; gender expression; high risk; hormonal contraception; hormone therapy; improved; innovation; male; men who have sex with men; pre-exposure prophylaxis; preventive intervention; programs; racial minority; safety outcomes; sex; skills; social; social factors; standard of care; theories; transgender; transgender men; transgender women; uptake; young man

PROJECT SUMMARY/ABSTRACT Transgender women (TW) are one of the most vulnerable populations for acquiring HIV infection, and the scant available data on transgender men (TM) suggests they are also at risk. TW have accounted for only 0.2% of all participants in bio-behavioral HIV prevention trials using pre-exposure prophylaxis (PrEP), and TM have typically not been included. TW and TM adolescents have received even less attention in PrEP trials. Although tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), the FDA-approved PrEP drug, would not be expected to interact with cross-sex hormone therapy (cs-HT; estradiol and testosterone) based on known mechanisms and data from studies with hormonal contraceptives, there are no data that prove this. Given this lack of data, TW and TM youth on cs-HT have decreased PrEP uptake and adherence due to concerns that PrEP may reduce the effectiveness of cs-HT. To address these critical scientific gaps in PrEP safety for transgender youth and to plan for appropriate implementation we propose the following study in 3 integrated phases. In Phase 1, we will conduct a PK study exploring the interactions of cs-HT for both TW and TM on TDF/FTC. Simultaneously, in Phase 2, we will collect ethnographic data via focus groups and in-depth interviews to inform the development of a tailored gender-affirmative intervention to improve uptake and adherence to PrEP in transgender youth. In Phase 3, we will conduct a small demonstration trial of PrEP use in TW and TM youth, utilizing the ethnographically developed intervention to improve uptake and adherence, while also monitoring renal and bone safety outcomes. The project has the following specific aims: Aim 1: To evaluate the differential PK of TDF/FTC in a cohort of transgender youth on cs-HT by conducting a PK trial of daily TDF/FTC among 24 TW taking estradiol and 24 TM taking testosterone (ages 15-24 years) using video-based directly observed therapy (DOT) to insure daily adherence and maximize drug exposure. Aim 2: To develop a culturally, developmentally, and gender- affirmative intervention to increase uptake of and adherence to PrEP among TW and TM youth that is grounded in theory (Information-Motivation-Behavioral Skills Model of Behavior Change, Gender Affirmation, Empowerment Theory) and incorporates the PK data from Aim 1. We will conduct FGs with young TW (N=20- 30) and TM (N=20-30) and conduct IDIs with participants from the PK study (Total N=10-14). We will solicit continuous input and feedback from TW and TM on the project's Youth Advisory Board. Aim 3: To conduct a small randomized controlled trial within a PrEP demonstration project comparing the newly developed intervention with standard of care (SOC) in TW (N=50) and TM (N=50) ages 15-24 years.

项目总结/摘要 跨性别妇女是最容易感染艾滋病毒的人群之一， 关于变性男性（TM）的可用数据很少，这表明他们也有风险。TW只占了 使用暴露前预防（PrEP）的生物行为艾滋病毒预防试验的所有参与者的0.2%，以及TM 通常不包括在内。TW和TM青少年在PrEP试验中受到的关注更少。 虽然富马酸替诺福韦酯/恩曲他滨（TDF/FTC），FDA批准的PrEP药物， 基于已知的，预期与交叉性激素治疗（cs-HT;雌二醇和睾酮）相互作用 虽然激素避孕药的作用机制和研究数据不明确，但没有数据证明这一点。鉴于这种 由于缺乏数据，TW和TM青少年对cs-HT的摄取和依从性下降， PrEP可能会降低CS-HT的有效性。为了解决PrEP安全性方面的这些关键科学差距， 为制定适当的实施计划，我们建议在以下3个综合领域开展研究： 阶段。在第1阶段，我们将进行一项PK研究，探索TW和TM的cs-HT相互作用， TDF/FTC。同时，在第二阶段，我们将通过焦点小组收集人种学数据， 进行访谈，为制定有针对性的性别平等干预措施提供信息，以提高接受率， 在跨性别青年中坚持PrEP。在第三阶段，我们将在以下地区进行PrEP使用的小型示范试验： TW和TM青年，利用人种学开发的干预措施，以提高吸收和坚持， 同时还监测肾脏和骨骼安全性结果。 该项目具有以下具体目的：目的1：评价队列中TDF/FTC的差异PK 通过在24名服用雌二醇的TW和24名服用雌二醇的TW中进行每日TDF/FTC的PK试验， TM服用睾酮（年龄15 - 24岁），使用基于视频的直接观察治疗（DOT），以确保每天 坚持并最大化药物暴露。目标2：在文化、发展和性别方面， 积极干预，以增加TW和TM青年对PrEP的吸收和坚持， 以理论为基础（行为改变的信息-动机-行为技能模型，性别肯定， 授权理论），并纳入目标1的PK数据。我们将与年轻的TW（N = 20- 30)和TM（N = 20 - 30），并对PK研究的受试者进行IDI（总计N = 10 - 14）。我们将征求 荃湾和屯门对计划的青年顾问委员会持续提供意见和反馈。目标3：开展 在PrEP示范项目中进行的小型随机对照试验比较了新开发的 TW（N = 50）和TM（N = 50）年龄15 - 24岁的标准治疗（SOC）干预。

项目成果

Gender-Affirming Hormone Pharmacokinetics Among Adolescent and Young Adult Transgender Persons Receiving Daily Emtricitabine/Tenofovir Disoproxil Fumarate.

每日接受恩曲他滨/富马酸替诺福韦酯的青少年和年轻跨性别者的性别肯定激素药代动力学。

• DOI: 10.1089/aid.2022.0044
• 发表时间: 2022
• 期刊: AIDS research and human retroviruses
• 影响因子: 1.5
• 作者: Yager,Jenna;Brooks,KristinaM;Brothers,Jennifer;Mulligan,Kathleen;Landovitz,RaphaelJ;Reirden,Daniel;Malhotra,Meenakshi;Glenny,Carrie;Harding,Paul;Powell,Tina;Anderson,PeterL;Hosek,Sybil
• 通讯作者: Hosek,Sybil