A pharmacokinetic study evaluated the effect of masculinizing hormone therapy (MHT; i.e., testosterone enanthate 200 mg IM) on oral daily PrEP among trans men in Thailand (n=19). Testosterone enanthane was administered at baseline and every 2 weeks until week 12 while oral daily emtricitabine/tenofovir-DF -based PrEP (200/300 mg) was prescribed from week 6 until the end of the study at week 16. Pharmacokinetic sampling was performed at week 12 (PrEP with MHT) and week 16 (PrEP without MHT) to assess plasma concentrations of emtricitabine (FTC) and tenofovir (TFV). In addition, intracellular TFV-diphosphate (TFV-DP) and FTC triphosphate (FTC-TP) concentrations were assessed in peripheral blood mononuclear cells, rectal and cervical tissues. Geometric mean ratios (GMRs) (90% CI) of AUC0-24 and Cmax at week 12 and 16 (reference) were: TFV, 1.03 (0.96-1.11, p=0.55) and 1.17 (1.03-1.32, p=0.08); 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 vs 81.3 fmol/10^6 cells, p=0.19; C24 FTC-TP 3433.5 vs 4008.6 fmol/10^6 cells, p=0.47, rectal tissue (FTV-DP, 211.7 vs 61 fmol/mg, p=0.65 and FTC-TP, 8.33 vs 5.23 fmol/mg, p=0.11) and cervical tissue (TDF-DP 8.7 vs 5.9 fmol/mg, p=0.51 and FTC-TP, 30.3 vs 34.0 fmol/mg, p=0.28). In conclusion, plasma of TFV and FTC, and intracellular concentrations of TFV-DP and FTC-TP in PBMCs, rectal and cervical tissue were comparable when FTC/TDF-based PrEP was administered with and without MHT, suggesting no clinically significant drug interaction from MHT towards FTC/TDF-based PrEP. 

Sex hormones were measured in serum and tenofovir diphosphate in dried blood spots from transgender women and men on PrEP. Among 91 transgender women on stable estrogen, estradiol concentrations did not change significantly between week 0 and 12 in individuals taking PrEP (252.4 vs 222.3 pg/mL, p=0.81). Among 60 transgender men on stable testosterone, total testosterone concentrations did not change significantly between week 0 and 12 in individuals taking PrEP (352.7 vs 266.2 ng/dL, p=0.84). At week 12, there was no difference in tenofovir-DP in both transgender women and men not taking hormones compared to those taking hormone. There were no changes in satisfaction with or desired physical effects from hormones on gender transition. This study shows that transgender individuals both on and off hormone had similar tenofovir-DP concentrations in dried blood spots after 12 weeks of daily reported TDF/FTC PrEP use. Serum hormone concentrations were not affected by TDF/FTC PrEP use and there were no changes in the perceived effect on hormone in those taking PrEP.

The pharmacokinetics of testosterone administered either intramuscularly or subcutaneously was evaluated in adolescent transgender men (n=24, median [IQR] age: 21 [17-24]) receiving oral PrEP with emtricitabine/tenofovir-DF. Hormone concentrations were measured at baseline and after 2-3 weeks of daily PrEP dosing. The geometric mean AUC and Cmax for testosterone at baseline and on PrEP were 0.91 and 0.91 for total concentrations, and 0.88 and 0.89 for free concentrations. PrEP did not significantly alter serum estradiol pharmacokinetics in transgender women or free and total testosterone pharmacokinetics in transgender men.