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: 10388091
• 负责人: Sybil Hosek
• 金额: $ 56.52万
• 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/10388091
• 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.

项目摘要/摘要 变性妇女(TW)是感染艾滋病毒的最脆弱人群之一， 关于变性人(TM)的现有数据很少，这表明他们也处于危险之中。TW只占了 在使用暴露前预防(PrEP)和TM的生物行为艾滋病毒预防试验中，所有参与者的0.2% 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。 尽管FDA批准的PrEP药物替诺福韦富马酸/恩曲他滨(TDF/FTC)不会 有望与跨性激素治疗(cs-HT；雌二醇和睾酮)相互作用，基于已知的 机制和荷尔蒙避孕药研究的数据，没有数据证明这一点。鉴于此， 缺乏数据，TW和TM青年对cs-HT的摄取率和依从性下降，原因是担心 PREP可能会降低cs-HT的疗效。为了解决PrEP安全方面的这些关键科学差距， 为了规划适当的实施，我们建议在3个综合项目中进行以下研究 阶段。在第一阶段，我们将进行PK研究，探索cs-HT在TW和TM上的相互作用 TDF/FTC。同时，在第二阶段，我们将通过重点小组和深入的 面谈，以了解制定有针对性的性别平权干预措施，以提高理解和 变性人青年对PrEP的坚持。在第3阶段，我们将进行PrEP在 TW和TM青年，利用人种学制定的干预措施，提高吸纳和坚持， 同时还监测肾脏和骨骼的安全结果。 该项目有以下具体目标：目标1：评估TDF/FTC在队列中的差异PK 通过对24名服用雌二醇的TW和24名服用雌二醇的TW进行每日TDF/FTC的PK试验，了解变性青年服用cs-HT的情况 TM服用睾酮(年龄15-24岁)，使用基于视频的直接观察疗法(DOT)来确保每天 坚持并最大限度地增加药物暴露。目标2：发展一种文化、发展和性别-- 平权干预，以增加TW和TM青年对PrEP的接受和遵守，即 以理论为基础(信息-动机-行为技能行为改变模型，性别肯定， 赋权理论)，并纳入了来自目标1的PK数据。我们将与年轻的TW(N=20- 30)和TM(N=20-30)，并与PK研究的参与者(总N=10-14)进行IDI。我们将征集 TW和TM对该项目青年咨询委员会的持续投入和反馈。目标3：开展 PrEP示范项目内的小型随机对照试验，比较新开发的 对15-24岁的TW(N=50)和TM(N=50)进行标准护理(SOC)干预。