Exploring potential drug−drug interactions between masculinizing hormone therapy and oral pre-exposure prophylaxis (F/TDF and F/TAF) among transgender men (iMACT study): a randomized, open-label pharmacokinetic study in Thailand

Abstract

Introduction

Concerns regarding potential drug−drug interactions (DDIs) between hormone therapy and pre-exposure prophylaxis (PrEP) may hinder PrEP use among transgender persons. Transgender men have often been overlooked in biomedical HIV research, and potential DDIs between masculinizing hormone therapy (MHT) and PrEP have not been addressed. We aimed to assess the potential DDIs between MHT and daily oral PrEP among transgender men.

Methods

Transgender men without HIV who never underwent oophorectomy were enrolled between May and October 2022. Participants were randomly assigned to receive emtricitabine-tenofovir disoproxil fumarate (F/TDF) or emtricitabine-tenofovir alafenamide (F/TAF) for daily oral PrEP. Intramuscular testosterone enanthate 200 mg was administered every 2 weeks from baseline to week 12, while oral PrEP was initiated at week 6 and continued until week 16. Pharmacokinetic (PK) sampling was conducted at weeks 4 and 12 to assess the impact of PrEP on MHT and at weeks 12 and 16 to evaluate the impact of MHT on PrEP. Plasma total testosterone, TAF, tenofovir (TFV) and FTC; tenofovir-diphosphate (TFV-DP) and emtricitabine-triphosphate (FTC-TP) concentrations in peripheral blood mononuclear cells (PBMCs) were measured in all participants. Cervical and rectal tissues were obtained in a subset of 20 participants (10 per group) to measure TDF-DP and FTC-TP.

Results

Thirty-nine participants (19 F/TDF and 20 F/TAF) completed the PK visits. No significant changes in the PK parameters of plasma total testosterone, TFV, FTC and TAF (for F/TAF group); urine TFV and FTC; and PBMC and rectal tissue TFV-DP and FTC-TP were observed when MHT and PrEP were administered together. Both TFV-DP and FTC-TP concentrations in cervical tissue were significantly lower when MHT was co-administered with F/TAF (TFV-DP: median [IQR] of 12.9 [6.78–14.56] fmol/mg at weeks 12 vs. 20.63 [7.47–53.43] fmol/mg at week 16, p = 0.04; and FTC-TP: 67.05 [27.24–77.24] fmol/mg vs. 120.43 [65.98–245.76] fmol/mg, p = 0.02).

Conclusions

Our findings across multiple anatomical compartments suggest that oral PrEP should not affect the effectiveness of MHT and that F/TDF-based PrEP should be effective when taken with MHT. However, further research is needed to assess the effectiveness of TAF-based PrEP in transgender men.

Clinical Trial Number

NCT04593680.