No impact of tenofovir/emtricitabine in estradiol exposure among transwomen on oral PrEP: results from the 12-week drug-drug interaction PrEParadas substudy


BACKGROUND: An important HIV prevention barrier for transwomen (TGW) is the concern that oral PrEP containing tenofovir (TDF) and emtricitabine (FTC) negatively affects the efficacy of feminizing hormone therapy (FHT). We aimed to assess the impact of PrEP on FHT among transwomen.
METHODS: We performed a drug-drug interaction substudy among TGW enrolled in a TDF/FTC daily oral PrEP and using FHT (estradiol valerate plus spironolactone) in a demonstration study for TGW and PrEP in Rio de Janeiro, Brazil (NCT03220152). Participants had a first pharmacokinetic (PK) assessment and initiated PrEP 15 days after FHT initiation (W0), followed by a second PK evaluation 12 weeks later (W12). Blood samples were collected prior and after the directly observed therapy (0.5, 1, 2, 4, 6, 8, and 24 hours). Estradiol and spironolactone PK parameters were estimated by non-compartmental analysis (Pharsight WinNonlin v. 7.6, Certara) and compared using Wilcoxon rank-sum test (alpha=0.05). We assessed PrEP adherence with DBS levels.
RESULTS: Among 24 transwomen that completed the study, median age was 26.0 years (23.0-34.5) and body mass index was 22.7 kg/m2 (20.6-26.0). Condomless anal sex in the last 6 months was reported by 92%. At W12, 6, 13, and 5 participants had DBS levels consistent with 7+ doses/week, 4-6 doses/week, <2 doses/week. Estradiol exposure did not differ between W0 and W12: AUC/D 596.0 (387.0-757.0) at W0 and 511.0 (367.0-707.0) h*pg/mL/mg at W12 (p-value= 0.056), Cmax 36.0 (24.0-48.0) at W0 and 28.3 (22.0-43.0) pg/mL at W12 (p-value=0.095). Although spironolactone AUC/D was significantly lower at W12 compared to W0 (2.8 [1.5-3.5] and 3.0 [2.1-5.1] h*ng/mL/mg, respectively, p-value=0.008), its Cmax did not differ between the two assessments (W0: 0.9 [0.7-1.3], W12: 0.8 [0.7-1.2] ng/mL, p-value= 0.96).
CONCLUSIONS: Our results reassure that oral PrEP and FHT may be used concomitantly. This adds to limited data on potential impact of oral PrEP on FHT among transwomen.