Background:
We previously reported that plasma total testosterone concentrations were comparable in trans men receiving oral daily PrEP with masculinizing hormone therapy (MHT). Herein, we report the impact of MHT on the PK parameters of oral daily F/TAF-based PrEP.
Methods:
iMACT was a PK study evaluating the potential drug-drug interactions between MHT and oral daily PrEP among trans men 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/TAF-based PrEP (200/25 mg) was prescribed from week 6 until the end of study at week 16. PK sampling was performed at 12 (PrEP with MHT) and 16 (PrEP without MHT) to assess plasma FTC, TAF, 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.
Results:
Among 20 participants, median (interquartile range [IQR]) age and body mass index were 27.5 (22.5-33) years and 23.8 (20.5-25.2) 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: TAF, 0.99 (0.80-1.21, p=0.93) and 1.00 (0.69-1.44, p=0.99); TFV, 1.03 (0.94-1.14, p=0.63) and 0.97 (0.84-1.43, p=0.64); and FTC, 1.02 (0.99-1.05, p=0.48) and 0.97 (0.85-1.12, p=0.80). There were no statistically significant differences in median TFV-DP and FTC-TP concentrations in PBMCs (C24 TFV-DP, 564.2 [IQR: 280.7-927.4] vs 631.9 [IQR: 347.1-727] fmol/106 cells, p=0.77; and C24 FTC-TP, 3341.2 [IQR: 2522.7-5352.9] vs 3888.3 [IQR: 2096.9-5592.5] fmol/106 cells, p=0.60) and rectal tissue (TFV-DP, 53.4 [30.3-185.4] vs 65.3 [32.8-92.3] fmol/mg, p=0.51; and FTC-TP, 7.6 [6.4-14.7] vs 7.7 [5.6-11.1] fmol/mg, p=0.51) between the two visits. However, both TFV-DP and FTC-TP concentrations in cervical tissue were significantly lower at week 12 than 16 (TFV-DP, 12.90 [6.8-14.6] vs 20.6 [7.5-53.4] fmol/mg, p=0.04; and FTC-TP, 67.1 [27.2-77.2] vs 120.4 [66.0-245.8] fmol/mg, p=0.02) (Figure).
Conclusions:
Plasma TAF, TFV, and FTC; and intracellular TFV-DP and FTC-TP levels in PBMCs and rectal tissue were comparable when F/TAF-based PrEP was co-administered with MHT. However, TFV-DP and FTC-TP concentrations trended significantly lower in cervical tissue.
