Sex Hormone Therapy and Tenofovir Diphosphate Concentration in Dried Blood Spots: Primary Results of the Interactions Between Antiretrovirals And Transgender Hormones Study

Abstract

Background: Sex hormone and preexposure prophylaxis (PrEP) drug interactions among transgender women (TGW), transgender men (TGM), and cisgender men (CGM) are not fully understood.

Methods: TGM and TGW on at least 6 months of stable sex hormone therapy containing testosterone or estradiol (respectively) were enrolled in a 4-week study of directly observed dosing of daily oral coformulated emtricitabine and tenofovir disoproxil fumarate (FTC/TDF). TFV-DP in dried blood spots and sex hormones in serum were measured at weekly intervals. TFV-DP was compared with 2- and 4-week samples from Directly Observed Therapy Dried Blood Spots (DOT-DBS) Study (NCT02022657).

Results: From May 2017 to June 2018, 24 TGM and 24 TGW were enrolled. Testosterone (total and free) and estradiol concentrations were comparable before and after 4 weeks of PrEP use in TGM and TGW, respectively. Historical controls included 17 cisgender women (CGW) and 15 CGM. TFV-DP concentrations at week 4 were comparable between TGW and TGM (mean difference, -6%; 95% confidence interval [CI], -21% to 12%; P = .47), comparable between TGW and CGM (mean difference, -12%; 95% CI, -27% to 7%; P = .21) and were lower among TGM compared with CGW (mean difference, -23%; 95% CI, -36% to -7%; P = .007). All persons in all groups were projected to reach the TFV-DP threshold that has been associated with high protection from human immunodeficiency virus.

Conclusions: CGM, TGM, and TGW had comparable TFV-DP concentrations in dried blood spots after 4 weeks of directly observed daily FTC/TDF PrEP use. Serum hormone concentrations were not affected by FTC/TDF PrEP use.

Clinical trials registration: NCT04050371.

Keywords: HIV; pharmacokinetics; preexposure prophylaxis; sex hormones; transgender.

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Figures

Figure 1.

Interactions Between Antiretrovirals And Transgender Hormones Study (iBrEATHe) consort diagram. There were 24 transgender women and 24 transgender men enrolled in a stratified enrollment design.

Figure 2.

Box plots of hormone concentrations before and after emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) preexposure prophylaxis dosing. Serum estradiol concentrations (A) and total testosterone concentrations (B) are depicted on a natural logarithmic scale before FTC/TDF dosing and after 4 weeks of directly observed daily dosing among TGM and TGW. The boxes represent median values and the interquartile range, and the whiskers represent the 95% confidence intervals; dots beyond the whiskers are outliers. There are no statistically significant differences. Abbreviations: TGM, transgender men; TGW, transgender women.

Figure 3.

TFV-DP concentrations in dried blood spots after 4 weeks of directly observed daily dosing. The boxes represent median values and the interquartile range, and the whiskers represent the 95% confidence intervals; dots beyond the whiskers are outliers. Abbreviations: CGM, cisgender men; CGW, cisgender women; TFV-DP, tenofovir diphosphate; TGM, transgender men; TGW, transgender women.