Background:
Potential drug-drug interactions between masculinizing hormone (MHT) and oral PrEP in trans men is not well understood. We previously observed that plasma total testosterone concentrations were comparable when oral daily PrEP was administered with and without MHT. Herein, we report the impact of MHT on the PK parameters of F/TDF in trans men using oral daily PrEP.
Methods:
iMACT was a PK study evaluating the potential drug-drug interactions (DDI) between MHT and oral PrEP among trans men in Thailand. Trans men who had not undergone oophorectomy were enrolled between May and October 2022. MHT (testosterone enanthate 200 mg intramuscular) was administered at baseline and every 2 weeks until week 12, while oral daily F/TDF-based PrEP (200/300 mg) was initiated at week 6 and prescribed until the end of study at week 16. PK sampling was conducted at week 12 (PrEP with MHT) and 16 (PrEP without MHT). Plasma FTC and tenofovir (TFV); and intracellular TFV-diphosphate (TFV-DP) and FTC triphosphate (FTC-TP) concentrations in peripheral blood mononuclear cells (PBMCs), rectal, and cervical tissues were assessed.
Results:
19/20 participants completed the PK visits and were included in this analysis. Median (IQR) age and body mass index were 34 (28-39) years and 22.1 (21.3-24.7) kg/m2, respectively. The geometric mean ratios (GMRs) (90%CI) of area under the concentration-time curve from 0 to 24 hours (AUC0-24) and maximum concentration (Cmax) at week 12 and 16 (reference) were as follows: TFV, 1.03 (0.96-1.11, p=0.55) and 1.17 (1.03-1.32, p=0.08); and FTC, 1.05 (1.00-1.09, p=0.12) and 1.09 (1.00-1.18, p=0.17). Median pre-dose TFV-DP and FTC-TP concentrations were not significantly different between week 12 and 16 in PBMCs (C24 TFV-DP, 83.6 [72.0-102.3] vs 81.3 [36.1-100.8] fmol/106 cells, p=0.19; and C24 FTC-TP, 3433.5 [2692.9-4635.5] vs 4008.6 [2608.3-5025.2] fmol/106 cells, p=0.47), rectal tissue (TFV-DP, 211.7 [82.4-517.7] vs 61 [33.1-388.7] fmol/mg, p=0.65; and FTC-TP, 8.33 [4.9-11.9] vs 5.23 [4.4-7.2], fmol/mg, p=0.11), and cervical tissue (TDF-DP, 8.7 [4.0-12.4] vs 5.9 [2.8-9.1] fmol/mg, p=0.51; and FTC-TP, 30.3 [5.1-143.0] vs 34.0 [29.0-153.8] fmol/mg, p=0.28) (Figure).
Conclusions:
Plasma levels of TFV and FTC, and intracellular concentrations of TFV-DP and FTC-TP in PBMCs, rectal and cervical tissue, were comparable when F/TDF-based PrEP was administered with and without MHT, suggesting no clinically significant DDI from MHT towards F/TDF-based PrEP.
