LAUSR

The transgender community has expressed concerns regarding drug-drug interactions between HIV-pre-exposure prophylaxis (PrEP) and gender-affirming hormones. In this study, we evaluated emtricitabine (F, FTC)/tenofovir disoporoxil fumarate (TDF) pharmacokinetics among adolescent and young adult transgender persons receiving gender-affirming hormone therapy (GAHT). This was a prospective, observational study among transgender women (TW) and men (TM) without HIV ages 15-24 receiving GAHT (estradiol with/without spironolactone, or testosterone). Participants received one month of directly observed daily F/TDF. Weekly convenience blood samples were collected for plasma TFV and FTC, and intracellular TFV-diphosphate (TFV-DP) and FTC-triphosphate (FTC-TP) in peripheral blood mononuclear cells (PBMC) and dried blood spots (DBS). After 2-3 weeks of F/TDF dosing, intensive PK sampling was conducted. PK parameters were estimated using noncompartmental methods. Data were log-transformed and compared between TM and TW, and to historical data among cisgender adults. Plasma TFV exposures were similar between TM and TW (GMR [95% CI]: 1.06 [0.89-1.28]), whereas FTC plasma exposures were 21% higher in TM vs. TW (95% CI: 1.07-1.38). TFV-DP in PBMC and DBS and FTC-TP in DBS did not differ between TM vs. TW after controlling for CrCl, but FTC-TP in PBMC remained 46% (95% CI: 1.15-1.86) higher in TM vs. TW. All PK exposures were within expected ranges based on historical studies. TM had higher FTC exposures compared with TW, but overall plasma and intracellular exposures for both drugs were within the range of historical studies suggesting high PrEP efficacy will be retained in adolescent and young adult transgender persons.