Plasma bictegravir/emtricitabine/tenofovir alafenamide concentrations in transgender women with HIV on oestrogen‐based gender‐affirming hormone therapy in comparison to cisgender women living with HIV

5 Background: Oestrogen-based gender-affirming hormone therapy (E-GAHT) typically consists of an oestrogen ± an anti-androgen and is essential for many transgender women. However, there is concern regarding drug–drug interactions (DDIs) between antiretroviral therapy (ART) and E-GAHT. This study's objective was to investigate the pharmacokinetics of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in transgender women taking E-GAHT compared to pre-menopausal cisgender women. Methods: We conducted a parallel group study in adult transgender women with HIV taking ART (transgender group) and cisgender women with HIV taking ART (control group). All participants were on suppressive ART for at least 6 months prior to and either taking or switched to BIC/FTC/TAF at entry. All participants in the transgender group were taking at least 2 mg/day of oral estradiol and anti-androgen therapy and could not have any E-GAHT medication changes for at least 3 months prior to entry. At the Month 2 visit, blood samples were collected prior to ART and E-GAHT dosing (if applicable) and then at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 h post-dose. BIC, FTC and TAF plasma concentrations were measured using a validated LC-MC/MS assay. Maximum (Cmax) and minimum (Cmin) concentrations were observed, and area under the concentration-time curve (AUC) over 24 h was calculated by non-compartmental methods. Data are presented as median (IQR) and compared between transgender and control groups by geometric mean ratio (GMR) with 90% confidence intervals (CI). Results: A total of 25 participants were enrolled, 10 transgender women and 15 cisgender women. E-GAHT consisted of a median estradiol dose of 4 mg (4, 4). Anti-androgen therapy included spironolactone (n = 6), cyproterone (n = 2), hypopituitarism (n = 1) and orchidectomy (n = 1). Median BIC Cmax, Cmin and AUC for the transgender group were 9.1 mcg/mL (8.1, 9.6), 2.6 mcg/mL (1.1, 3.1) and 119.5 h*mcg/mL (86.6, 141.2), respectively, compared to 7.2 mcg/mL (6.4, 9), 1.9 mcg/mL (1.4, 3.4) and 123.9 h*mcg/mL (79.7, 133.2), respectively, for the Control group. BIC PK parameters were similar between groups (GMR [90% CI]: 1.1 [0.9, 1.4], 1 [0.6, 1.7], and 1 [0.8, 1.3], respectively). Median FTC Cmax, Cmin and AUC for the transgender group were 2 mcg/mL (1.3, 2.5), 0.1 mcg/mL (0.1, 0.1) and 10.7 h*mcg/mL (8.7, 14), respectively, compared to 2 mcg/mL (1.6, 2.3), 0.1 mcg/mL (0.1, 0.1) and 11 h*mcg/mL (9.8, 15.6), respectively, for the control group. FTC PK parameters were similar between groups (GMR [90% CI]: 0.9 [0.8, 1.2], 1.1 [0.8, 1.5], and 1 [0.8, 1.2], respectively). Median TAF Cmax, Cmin and AUC for the transgender group were 164 ng/mL (90, 335), 0.5 ng/mL (0.5, 0.5) and 143 h*ng/mL (116, 320), respectively, compared to 250 ng/mL (132, 396), 0.5 ng/mL (0.5, 0.5) and 230 h*ng/mL (189, 394), respectively, for the control group. TAF PK parameters were similar between groups (GMR [90% CI]: 0.7 [0.4, 1.2], 1 [1, 1], and 0.7 [0.5, 1], respectively). All participants remained virally suppressed (HIV RNA < 200 copies/mL) throughout the study. Conclusion: BIC/FTC/TAF plasma pharmacokinetics were similar between groups, indicating no clinically significant effect of oral E-GAHT on BIC/FTC/TAF.