Emtricitabine (F), tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) do not have relevant drug interactions with low-dose hormones used for contraception. The current analysis explored PK as well as efficacy and safety of transwomen receiving either F/TAF or F/TDF in the DISCOVER trial, the majority of whom were taking high-dose, gender-affirming, hormonal therapy.
Overall, 74 transwomen at risk of HIV were randomized 1:1 to receive blinded F/TAF or F/TDF once daily in DISCOVER. Efficacy and safety results are summarized. TFV-DP and FTC-TP PBMC trough levels (Ctau; defined as 20 to 28 hours postdose) were evaluated at steady-state (W4) and compared between transwomen taking high-dose hormones concomitantly with F/TAF (N=17) and a randomly pre-selected, representative group of MSM randomized to F/TAF not using high-dose hormones (N=161) using geometric least squares mean (GLSM) ratios and 90% confidence intervals (CIs). Comparisons were made using a lack of PK alteration boundary of 50 to 200% to identify potentially clinically relevant differences. Levels of TFV-DP and FTC-TP with F/TDF in transwomen on high-dose hormones (N=10) were compared descriptively to levels in MSM randomized to F/TDF (N=155) due to a smaller sample size.
No transwomen acquired HIV. Transwomen had similar numerical improvements in dipstick proteinuria and markers of tubular proteinuria as MSM. No transwomen developed clinically significant proteinuria (UPCR>200 mg/g). There were no differences between F/TAF and F/TDF in change from baseline in weight or eGFR in transwomen. GLSM ratios and 90% CIs for comparisons of PBMC TFV-DP and FTC-TP levels with F/TAF between transwomen taking high-dose hormones and MSM were within the 50 to 200% boundary, indicating no clinically significant interaction. In transwomen taking F/TDF and high-dose hormones, TFV-DP and FTC-TP levels were comparable to MSM, suggesting no interaction (Table).
The absence of infections suggests that both F/TAF and F/TDF were effective for HIV prevention in transwomen. Both F/TAF and F/TDF were safe and well-tolerated in transwomen and MSM. No clinically meaningful differences in PBMC TFV-DP and FTC-TP levels with F/TAF or F/TDF were observed between transwomen taking high-dose hormone therapy and MSM, suggesting that both F/TAF and F/TDF are effective and safe options for PrEP in transwomen on gender-affirming, high-dose hormone therapy.