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. 2024 Jan 31;9(1):46-52.
doi: 10.1089/trgh.2022.0048. eCollection 2024 Feb.

Gender Affirming Hormones Do Not Affect the Exposure and Efficacy of F/TDF or F/TAF for HIV Preexposure Prophylaxis: A Subgroup Analysis from the DISCOVER Trial

Michelle S Cespedes  1 , Moupali Das  2 , Jenna Yager  2 , Maria Prins  3 , Ivanka Krznaric  4 , Jan de Jong  2 , Deqing Xiao  2 , Yongwu Shao  2 , Pamela Wong  2 , Alexander Kintu  2 , Christoph Carter  2 , Elske Hoornenborg  5 , Peter Ruane  6 , John Phoenix  7 , Islam Younis  2 , Jason Halperin  8
Affiliations

Gender Affirming Hormones Do Not Affect the Exposure and Efficacy of F/TDF or F/TAF for HIV Preexposure Prophylaxis: A Subgroup Analysis from the DISCOVER Trial

Michelle S Cespedes et al. Transgend Health. .

Abstract

Purpose: Transgender women are disproportionately affected by HIV and are underutilizing preexposure prophylaxis (PrEP). The lower uptake of PrEP by transgender women may be, in part, owing to the perception that taking PrEP may lower the efficacy of gender-affirming hormone therapy (GAHT) or to provider concerns that GAHT may lower the efficacy of PrEP.

Methods: DISCOVER was a randomized, double-blind, noninferiority trial comparing emtricitabine (FTC, F) and tenofovir alafenamide (F/TAF) versus emtricitabine and tenofovir disoproxil fumarate (F/TDF) as PrEP among transgender women and cisgender men who have sex with men (MSM). This nested substudy of the DISCOVER trial compared the exposure of the active intracellular metabolites of FTC and tenofovir (TFV), FTC triphosphate (FTC-TP) and TFV diphosphate (TFV-DP), in peripheral blood mononuclear cells (PBMC) among transgender women receiving GAHT versus MSM within the F/TAF and F/TDF groups.

Results: Our results demonstrate that TFV-DP and FTC-TP levels in PBMC were comparable between transgender women on GAHT and MSM receiving F/TAF, and between transgender women on GAHT and MSM receiving F/TDF. TFV-DP concentrations remained above the EC90 of 40 fmol/106 cells across all groups. No clinically significant drug-drug interactions of GAHT were observed with either F/TAF or F/TDF in this subanalysis.

Conclusions: These findings are consistent with the clinical pharmacology of GAHT, FTC, TDF, and TAF reported in previous studies, and support the continued use of F/TAF and F/TDF for PrEP in transgender women.

Clinicaltrials.gov registration number: NCT02842086.

Keywords: DISCOVER trial; drug–drug interaction; gender affirming hormones; preexposure prophylaxis; transgender women.

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Conflict of interest statement

M.D., J.Y., J.d.J., D.X., Y.S., P.W., A.K., C.C., and I.Y. are employed by Gilead Sciences and hold stock in the company. All other authors are investigators on this Gilead sponsored study.

Figures

FIG. 1.
FIG. 1.
Steady-state trough concentrations of TFV-DP and FTC-TP (fmol/106 cells) in PBMC in transgender women taking gender-affirming hormones and cisgender MSM after administration of F/TAF (200/25 mg) or F/TDF (200/300 mg). Symbols represent individual values for TFV-DP (A, B) and FTC-TP (C, D); solid lines depict median and Q1 and Q3 interquartile range. Data from F/TAF arm is plotted on the left (A, C); F/TDF arm on the right (B, D). Ctau, trough concentration; F or FTC, emtricitabine; FTC-TP, emtricitabine triphosphate; MSM, men who have sex with men; PBMC, peripheral blood mononuclear cells; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate; TFV-DP, tenofovir diphosphate.
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References

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