Impact of feminizing hormone therapy on tenofovir and emtricitabine plasma pharmacokinetics: A nested drug-drug interaction study in a cohort of Brazilian transgender women using HIV pre-exposure prophylaxis

Abstract

Objectives: Potential interactions between feminizing hormone therapy (FHT) and pre-exposure prophylaxis (PrEP) may be a barrier to PrEP use among transgender women (TGW). We aimed to assess the impact of FHT on PrEP plasma pharmacokinetics (PK) among TGW. Methods: This was a PK substudy of the effects of FHT on tenofovir disoproxil fumarate/emtricitabine nested to a trans-specific PrEP demonstration study (NCT03220152). Participants were assigned to receive PrEP only (noFHT) or standardized FHT (sFHT; oestradiol valerate 2-6mg plus spironolactone 100-300mg) plus PrEP for 12weeks, after which they could start any FHT (aFHT). Short-and long-Term PK assessment occurred at Weeks 12 and 30-48, respectively (plasma samples prior and 0.5, 1, 2, 4, 6, 8 and 24h after dose). Non-compartmental PK parameters of tenofovir and emtricitabine were compared as geometric mean ratios (GMRs) between noFHT and PrEP and FHT (sFHT at short-Term PK; aFHT at long-Term PK) participants. Results: No differences in tenofovir and emtricitabine plasma PK parameters were observed between the short-Term PK of noFHT (n12) and sFHT participants (n18), except for emtricitabine Cmax [GMR: 1.15 (95% CI: 1.01-1.32)], or between noFHT short-Term PK and aFHT long-Term PK (n13). Most participants were on oestradiol valerate 2mg at the short-Term PK (56%) and 4mg at the long-Term PK (54%). Median (IQR) oestradiol levels were 56.8 (43.2-65.4)pg/mL at short-Term PK (sFHT) and 44.8 (24.70-57.30)pg/mL at long-Term PK (aFHT). No participants in this analysis seroconverted during the study. Conclusions: Our results indicate no interaction of FHT on tenofovir levels, further supporting PrEP use among TGW using FHT.