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

J Antimicrob Chemother. 2022 Sep 30;77(10):2729-2736. doi: 10.1093/jac/dkac229.

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 2-6 mg plus spironolactone 100-300 mg) plus PrEP for 12 weeks, 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 24 h 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 (n = 12) and sFHT participants (n = 18), except for emtricitabine Cmax [GMR: 1.15 (95% CI: 1.01-1.32)], or between noFHT short-term PK and aFHT long-term PK (n = 13). Most participants were on oestradiol valerate 2 mg at the short-term PK (56%) and 4 mg 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents* / therapeutic use
  • Brazil
  • Cohort Studies
  • Drug Interactions
  • Emtricitabine / therapeutic use
  • Estradiol / therapeutic use
  • Female
  • HIV Infections* / drug therapy
  • HIV Infections* / prevention & control
  • Humans
  • Pre-Exposure Prophylaxis* / methods
  • Spironolactone / therapeutic use
  • Tenofovir / pharmacokinetics
  • Transgender Persons*

Substances

  • Anti-HIV Agents
  • Spironolactone
  • Estradiol
  • Tenofovir
  • Emtricitabine