Background:
Feminizing hormone therapy (FHT) is common among transgender women (TGW) receiving PrEP. To evaluate the potential drug-drug interaction (DDI) between FHT and emtricitabine (FTC)/tenofovir alafenamide (TAF)-based PrEP, we assessed the pharmacokinetics (PK) of FTC, TAF, tenofovir (TFV) and estradiol (E2) among TGW receiving FHT in Thailand.
Methods:
Twenty TGW who had not undergone orchiectomy and had not received injectable FHT within 3 months were enrolled between January and February 2022. FHT (estradiol valerate 2 mg and cyproterone acetate 25 mg) was prescribed to participants at baseline until week 9, while PrEP (FTC 200 mg/TAF 25 mg) was initiated at week 3 until week 12. Intensive PK sampling was performed at weeks 3 (FHT only) and 9 (PrEP and FHT) for E2; and weeks 9 (PrEP and FHT) and 12 (PrEP only) for plasma FTC, TAF, and TFV. Blood bioavailable testosterone, FSH, and LH were also measured.
Results:
18/20 participants completed the PK visits and were included in this analysis. Median (interquartile range [IQR]) age and body mass index were 28 (23-32) years and 20.8 (19.9-21.9) kg/m2, respectively. The area under the curve (AUC) and maximum concentration (Cmax) geometric mean ratios (GMRs) (90%CI) at week 3 (reference) and week 9 for E2 were 0.80 (0.72-0.90, p=0.002) and 1.11 (0.94-1.31, p=0.23), respectively. The AUC and Cmax GMRs at week 9 and week 12 (reference) were as follows: FTC, 0.92 (0.88-0.97, p=0.009) and 0.93 (0.84-1.03, p=0.24); TAF, 1.05 (0.83-1.33, p=0.73) and 1.14 (0.85-1.52, p=0.46); and TFV, 0.92 (0.88-0.97, p=0.01) and 0.97 (0.89-1.05, p=0.50) (Figure). No significant changes in bioavailable testosterone, FSH, and LH between weeks 3 and 9 were observed (bioavailable testosterone, median [IQR] 0.031 [0.025-0.120] vs 0.024 [0.006-0.122], p=0.17; FSH, 0.75 [0.6-1.3] vs 0.85 [0.4-1.6], p=0.24; and LH, 0.52 [0.21-0.86] vs 0.44 [0.25-0.79], p=0.95. No participants discontinued the study due to a reported adverse event. There were no significant changes in creatinine clearance and alanine aminotransferase levels over the study period.
Conclusions:
Plasma E2, FTC and TFV exposures trended lower when FTC/TAF was administered with FHT; however, the AUC and Cmax GMRs of FTC and TFV were within the bioequivalence range, indicating no clinically significant DDI from FHT towards FTC/TAF-based PrEP. Intracellular and tissues rectal measurements of TFV-DP and FTC-TP levels are ongoing.
