In transgender women with HIV, feminizing hormone therapy may decrease the efficacy of pre-exposure prophylaxis (PrEP), according to a small study published in Clinical Infectious Diseases.1

High doses of estradiol may affect the pharmacology of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) by increasing nucleotidases.2 Increased 5’nucleotidase activity can increase deoxyadenosine-triphosphate (dATP) and/or decrease tenofovir-diphosphate.3 Because nucleotide balance is an important effector of TDF/FTC potency, researchers explored whether feminizing hormone therapy alters PrEP pharmacology in blood and rectal tissue of transgender women compared with tissue from cisgender women and men.1

In this prospective, observational study (ClinicalTrials.gov identifier: NCT02983110), researchers enrolled participants receiving TDF/FTC as part of their suppressive HIV treatment into 3 groups: transgender women receiving feminizing hormone therapy (n=4), postmenopausal cisgender women (intended as a low estrogen control group; n=4), and cisgender men (n=2). Blood and rectal tissue samples were collected at baseline. Participants adhered to a low fiber diet for 72 hours followed by clear liquids only for 12 hours prior to sampling. Adherence was assessed by 30-day self-report of missed doses and 5-day dosing record. A follow-up visit was conduced within 14 days.

Results showed that the median tenofovir-diphosphate relative to dATP was 7-fold lower in the rectal tissue of transgender women compared with cisgender women and men (P <.05) and decreased with increasing concentrations of estradiol and progesterone (ρ = -0.79 and -0.70, respectively; P <.05). This was not the case when evaluating peripheral blood mononuclear cells. Despite altered pharmacology, HIV RNA and DNA were not different in the rectal tissue.

Emtricitabine-triphosphate relative to deoxycytidine-triphosphate did not differ in blood or rectal tissue between transgender women and cisgender participants.

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This study “confirm[s] in vitro studies suggesting [feminizing hormone therapy] may decrease TDF/FTC’s potency and indicate the degree of feminization may be an important consideration,” noted the researchers. “Additional studies are needed to determine the clinical implications of our findings and whether PrEP dosing strategies should be reconsidered in [transgender women],” they concluded.

Disclosure: Frank Z. Stanczyk, PhD, serves as an independent consultant for Agile Therapeutics, TherapeuticsMD, Mithra Pharmaceuticals, and Dr. Reddys Laboratories.

References

  1. Cottrell ML, Prince HMA, Schauer AP, et al. Decreased tenofovir diphosphate concentrations in a transgender female cohort: implications for HIV pre-exposure prophylaxis (PrEP) [published online April 9, 2019]. Clin Infect Dis. doi:10.1093/cid/ciz290
  2. Shen Z, Fahey J V, Bodwell JE, et al. Estradiol regulation of nucleotidases in female reproductive tract epithelial cells and fibroblasts. PLoS One. 2013;8(7):e69854.
  3. Hunsucker SA, Mitchell BS, Spychala J. The 5’-nucleotidases as regulators of nucleotide and drug metabolism. Pharmacol Ther. 2005;107(1):1-30.