No significant drug-drug interaction between oral TAF-based PrEP and feminizing hormone therapy among transgender women in Thailand: the iFACT-3 study

Abstract

Introduction: Concerns regarding potential drug-drug interaction (DDI) between feminizing hormone therapy (FHT) and HIV pre-exposure prophylaxis (PrEP) may hinder PrEP use among transgender women. We assessed the potential DDI between FHT and emtricitabine-tenofovir alafenamide (F/TAF)-based PrEP among transgender women.

Methods: Transgender women without HIV who never underwent orchiectomy were enrolled between January and February 2022. Oral FHT (oestradiol valerate 2 mg and cyproterone acetate 25 mg) was initiated at baseline and continued until week 9, while oral PrEP (F/TAF 200/25 mg) was initiated at week 3 and continued until week 12. Intensive blood sampling was performed at weeks 3 and 9 to assess the impact of PrEP on FHT; and weeks 9 and 12 to assess the impact of FHT on PrEP. Pharmacokinetics (PKs) of plasma oestradiol (E2), TAF, tenofovir (TFV) and emtricitabine (FTC); urine TFV and FTC; and tenofovir-diphosphate (TFV-DP) and emtricitabine-triphosphate (FTC-TP) in peripheral blood mononuclear cells (PBMCs) and rectal tissues were assessed.

Results: Eighteen participants completed all PK visits. No significant differences in PK parameters for plasma E2, TAF and TFV were observed with FHT and F/TAF administration. The geometric mean of FTC AUC_0-24 at week 9 was 9% lower than at week 12, but the 90% CI (0.88-0.95) remained within the 80-125% range. There were no significant differences in PBMCs and rectal tissues TFV-DP and FTC-TP concentrations when F/TAF was administered with FHT.

Conclusions: No bidirectional clinically significant DDI between FHT and F/TAF-based PrEP was observed across systemic and local tissue anatomical compartments, supporting the use of oral F/TAF-based PrEP among transgender women.

Clinical trial number: NCT04590417.

Keywords: HIV prevention; Thailand; drug−drug interactions; feminizing hormone therapy; pre‐exposure prophylaxis; transgender women.

Figure 1

iFACT3 study scheme. Oral FHT was initiated at week 0 until week 9. Oral F/TAF‐based PrEP was initiated at week 3 and continued without interruption until the completion of study period at week 12. Intensive PK parameters of E2 were assessed at week 3 (FHT only) and week 9 (FHT + PrEP). Intensive PK parameters of ARVs were assessed at week 9 (FHT + PrEP) and week 12 (PrEP only). Abbreviations: ARVs, antiretroviral; E2, oestradiol; FHT, feminizing hormone therapy; FTC, emtricitabine; FTC‐TP, FTC‐triphosphate; PBMC, peripheral blood mononuclear cell; PK, pharmacokinetic; PrEP, pre‐exposure prophylaxis; TAF, tenofovir alafenamide; TFV, tenofovir; TFV‐DP, TFV‐diphosphate.

Figure 2

Median concentration time curves of plasma E2 at week 3 (without PrEP) and week 9 (with PrEP). Undetectable E2 (<5 pg/ml) imputed as 2.5 pg/ml. Abbreviation: E2, oestradiol.

Figure 3

Median concentration time curves of plasma TAF, TFV and FTC at week 9 (with FHT) and week 12 (without FHT). Undetectable TAF imputed as 0.05 ng/ml. Abbreviations: FHT, feminizing hormone therapy; FTC, emtricitabine; TAF, tenofovir alafenamide; TFV, tenofovir.