No significant drug−drug interaction between oral TAF-based PrEP and feminizing hormone therapy among transgender women in Thailand: the iFACT-3 study

Introduction: Concerns regarding potential drug−drug interaction (DDI) between feminizing hormone therapy (FHT) and HIV pre-exposure prophylaxis (PrEP) may hinder PrEP use among transgender women. We assessed the potential DDI between FHT and emtricitabine-tenofovir alafenamide (F/TAF)-based PrEP among transgender women. Methods: Transgender women without HIV who never underwent orchiectomy were enrolled between January and February 2022. Oral FHT (oestradiol valerate 2 mg and cyproterone acetate 25 mg) was initiated at baseline and continued until week 9, while oral PrEP (F/TAF 200/25 mg) was initiated at week 3 and continued until week 12. Intensive blood sampling was performed at weeks 3 and 9 to assess the impact of PrEP on FHT; and weeks 9 and 12 to assess the impact of FHT on PrEP. Pharmacokinetics (PKs) of plasma oestradiol (E2), TAF, tenofovir (TFV) and emtricitabine (FTC); urine TFV and FTC; and tenofovir-diphosphate (TFV-DP) and emtricitabine-triphosphate (FTC-TP) in peripheral blood mononuclear cells (PBMCs) and rectal tissues were assessed. Results: Eighteen participants completed all PK visits. No significant differences in PK parameters for plasma E2, TAF and TFV were observed with FHT and F/TAF administration. The geometric mean of FTC AUC0−24 at week 9 was 9% lower than at week 12, but the 90% CI (0.88−0.95) remained within the 80–125% range. There were no significant differences in PBMCs and rectal tissues TFV-DP and FTC-TP concentrations when F/TAF was administered with FHT. Conclusions: No bidirectional clinically significant DDI between FHT and F/TAF-based PrEP was observed across systemic and local tissue anatomical compartments, supporting the use of oral F/TAF-based PrEP among transgender women. Clinical Trial Number: NCT04590417.