Transgender Youth and PrEP: PK, Safety, Uptake & Adherence - Demonstration Project

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, the investigators propose the following study in 3 integrated phases. In Phase 1, investigators will conduct a PK study exploring the interactions of cs-HT for both TW and TM on TDF/FTC. Simultaneously, in Phase 2, investigators 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, investigators 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.

• PrEP Demonstration Project (Behavioral): In phase 2, a culturally, developmentally, and gender-affirmative intervention to increase uptake of and adherence to PrEP among TW and TM youth will be developed by incorporates the PK data from phase 1 and data gathered from focus groups and in-depth interviews with young transgender women and transgender men. During phase 3, this intervention will be given to the experimental arm and tested versus a standard-of-care control group.

Primary outcomes

• PrEP Acceptability Questionnaire [48 weeks]: Acceptability and feasibility of PrEP among TM and TW youth will be measured; details unavailable at the current time as specific study has yet to be developed.
• Tenofovir diphosphate levels [48 weeks]: Adherence to PrEP among TM and TW youth will be measured; details unavailable at the current time as specific study has yet to be developed.

Sex: All, ages: 15 Years to 24 Years, accepts healthy volunteers

Inclusion Criteria:

* Self-identification as a transgender individual \[As determined by the two-step process of gender identification whereby potential participants will be asked their gender identity and sex assigned at birth\]
* HIV-uninfected by EIA and viral load within 7 days of study entry
* Creatinine clearance ≥ 60 mL/min by Cockroft Gault for ages ≥18 years (Schwartz equation for those <18)
* Willing to comply with all study procedures
* On a stable dose of cs-HT for at least 2 months verified by clinical chart review and willing to not change doses for duration of PK study

Exclusion Criteria:

* Hospitalization within 30 days of study entry (elective procedures okay with team approval)
* Condition (medical, psychological, or social) that, in the opinion of the study investigators, would preclude the participant from completing study-required procedures
* Previous participation in an HIV vaccine study, unless the participant can document placebo arm assignment
* Use of TDF/FTC in the past 3 months

• Sybil Hosek, PhD, Principal investigator, Cook County Health

NIH grants: R01MH114753