EATG » Transgender females have lower tenofovir diphosphate concentrations

Transgender females have lower tenofovir diphosphate concentrations

Transgender females taking feminizing hormone therapy (FHT) have lower effective rectal tissue concentrations of tenofovir diphosphate active metabolites, compared with cisgender women and men, researchers report.

“The lower gastrointestinal tract of transgender women taking feminizing hormone therapy had a much lower balance of preexposure prophylaxis (PrEP’s) active metabolite relative to the endogenous substrate that HIV leverages for replication,” said Dr. Mackenzie L. Cottrell of the University of North Carolina at Chapel Hill Eshelman School of Pharmacy.

“This is important because this balance can impact PrEP’s ability to prevent cells within this tissue from becoming infected,” she told Reuters Health by email.

The potency of tenofovir diphosphate, the active metabolite of tenofovir, is inversely related to deoxyadenosine-triphosphate (dATP) concentrations. High doses of estradiol increase activity of 5′-nucleotidase enzymes, which, in turn, can increase dATP and/or decrease tenofovir diphosphate concentrations, thereby reducing the potency of tenofovir-based PrEP.

Dr. Cottrell and colleagues explored whether FHT alters the pharmacology of tenofovir diphosphate in blood and rectal tissue of transgender women compared with cisgender women and men, all of whom were taking a fixed-dose-combination tablet of tenofovir disoproxil fumarate and emtricitabine for either HIV suppression or PrEP.

Blood and rectal tissue concentrations of parent drugs, their metabolites and dATP concentrations were similar across the groups.

In contrast, the median ratio of tenofovir diphosphate to dATP was seven-fold lower in rectal tissue (but not peripheral blood mononuclear cells (PBMCs)) of transgender women versus cisgender participants, the researchers report in Clinical Infectious Diseases, online April 9.

Moreover, the ratio of tenofovir diphosphate to dATP correlated inversely with estradiol levels, which were highest among transgender women.

Despite significantly lower rectal ratios of tenofovir diphosphate to dATP and transgender women, the researchers did not find increased rectal HIV RNA or DNA.

“Additional studies are needed to determine the clinical implications of our findings and whether PrEP dosing strategies should be reconsidered in transgender women,” they conclude.

“I think these preliminary data indicate that until we fully characterize this potential drug interaction, we should make sure not to consider transgender women and cisgender men who have sex with men as equivalent when it comes to adherence messaging for PrEP,” Dr. Cottrell said. “It is possible that transgender women have less forgiveness for missed PrEP doses due to feminizing hormone therapy.”

“Physicians prescribing PrEP for transgender women who are taking feminizing hormone therapy should assist their patient in developing an environment that is maximally supportive of complete PrEP adherence, as well as provide adherence counseling and follow-up as frequently as possible,” she said.

SOURCE: https://bit.ly/2Dk9IYJ

Clin Infect Dis 2019.

By Will Boggs


 

Source:
Medscape
News categories: LGBTI, PrEP