Drug-drug interactions among Thai HIV-positive transgender women undergoing feminizing hormone therapy and antiretroviral therapy: the iFACT study

BACKGROUND: Drug-drug interactions (DDI) between feminizing hormone therapy (FHT) and antiretroviral therapy (ART) is a major concern among transgender women (TGW) that may lead to sub-optimal ART adherence and inappropriate FHT dosage. To evaluate potential DDI between FHT and ART, we measured intensive pharmacokinetic parameters (PK) of blood tenofovir (TFV), efavirenz (EFV), and estradiol (E2). METHODS: Twenty newly-diagnosed HIV-positive TGW were enrolled. FHT (estradiol valerate 2 mg and cyproterone acetate 25 mg) were prescribed at baseline until week 5 and restarted at week 8. ART (tenofovir disoproxil fumarate/emtricitabine/efavirenz 300/200/600 mg) was initiated at week 3. Intensive E2 PK were measured at weeks 3 (without ART) and 5 (with ART), and intensive TFV and EFV PK were measured at weeks 5 (with FHT) and 8 (without FHT). RESULTS: Median (IQR) age and body mass index were 25.5 (22.5-31.0) years and 20.6 (19.3-23.1) kg/m2, respectively. The differences in GMR (90%CI) of E2 AUC, Cmax, and C24 at week 5 versus week 3 were 0.72 (0.64-0.81), p<0.001; 0.81 (0.72-0.92), p=0.006; and 0.64 (0.50-0.83), p=0.004, respectively. The differences in GMR (90%CI) of TFV AUC, C24, and EFV C24 at week 5 versus week 8 were 0.86 (0.80-0.93), p=0.002; 0.83 (0.75-0.93), p=0.006; and EFV C24 was 0.91 (0.85-0.97), p=0.02, respectively. CONCLUSIONS: E2 PK was significantly lowered in the presence of TDF/FTC/EFV, and some lower TFV and EFV PK in the presence of FHT among HIV-positive TGW. Further studies should determine whether these reductions are clinically significant and evidenced when other FHT or ART regimens are used.