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.

项目概要/摘要 跨性别女性（TW）是最容易感染艾滋病毒的人群之一， 关于跨性别男性 (TM) 的可用数据很少表明他们也面临风险。 TW 只占 0.2% 的 HIV 生物行为预防试验参与者使用暴露前预防 (PrEP) 和 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。 尽管 FDA 批准的 PrEP 药物富马酸替诺福韦二吡呋酯/恩曲他滨 (TDF/FTC) 不会 预计会与基于已知的跨性别激素疗法（cs-HT；雌二醇和睾酮）相互作用 激素避孕药的机制和研究数据，没有数据证明这一点。鉴于此 由于缺乏数据，TW 和 TM 青少年服用 cs-HT 的 PrEP 摄取率和依从性有所下降，原因是担心 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 跨性别青年并计划适当的实施，我们建议在 3 个综合领域进行以下研究 阶段。在第一阶段，我们将进行一项 PK 研究，探索 cs-HT 对 TW 和 TM 的相互作用 TDF/FTC。同时，在第二阶段，我们将通过焦点小组和深入收集人种学数据 访谈，为制定有针对性的性别平权干预措施提供信息，以提高吸收率和 跨性别青少年坚持 PrEP。在第三阶段，我们将进行 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来提高吸收率和依从性， 同时还监测肾脏和骨骼安全结果。 该项目有以下具体目标： 目标 1：评估队列中 TDF/FTC 的差异 PK 通过在 24 名服用雌二醇的跨性别青少年和 24 名服用 cs-HT 的跨性别青少年中进行每日 TDF/FTC 的 PK 试验 TM 使用基于视频的直接观察治疗 (DOT) 每天服用睾酮（年龄 15-24 岁） 坚持并最大限度地增加药物暴露。目标 2：培养一种文化上、发展上和性别上的 平权干预措施，以提高 TW 和 TM 青年对 PrEP 的接受和坚持 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、 赋权理论）并结合目标 1 的 PK 数据。我们将与年轻的 TW 进行 FG（N=20- 30) 和 TM (N=20-30)，并与 PK 研究的参与者进行 IDI（总 N=10-14）。我们将征集 TW 和 TM 对项目青年顾问委员会的持续投入和反馈。目标 3：开展 PrEP 示范项目中的小型随机对照试验比较了新开发的 对 15-24 岁的 TW (N=50) 和 TM (N=50) 进行标准护理 (SOC) 干预。

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