The World Health Organization (WHO) estimates that transgender women are 49 times more likely to be affected by HIV than other populations. Because transgender women are particularly vulnerable to HIV infection, scientists are striving to understand how feminizing hormones impact the efficacy of HIV medication. Unfortunately, this community is also underrepresented when it comes to enrollment in pre-exposure prophylaxis (PrEP) trials.

From 2017 to 2018, a team of investigators based at the Eshelman School of Pharmacy at the University of North Carolina at Chapel Hill conducted a study, published recently in Clinical Infectious Diseases, comprising 4 transgender women with HIV on feminizing hormones, 4 postmenopausal cisgender women with HIV (to avoid the confounding effects of natural estrogen), and 4 cisgender men (2 with HIV and 2 who were not infected with HIV). Participants took tenofovir disoproxil fumarate (TDF) plus emtricitabine (FTC) either as part of their antiretroviral therapy or PrEP regimens (the medication combination is also prescribed in the form of PrEP for non-infected individuals at risk of acquiring HIV).

Rectal tissue and blood samples were collected from each participant and tested for drug concentrations in vitro. The investigators learned that the medication metabolites, referred to as TFVdp:dATP, were 7 times lower in the rectal tissue of transgender women compared with the cisgender control group. Blood plasma levels of TFVdp:dATP, however, were not lower in the transgender group.
“I think that hormones modulate the spaces in those cells differently,” lead investigator Mackenzie Cottrell, PharmD, a research assistant professor in the Division of Pharmacotherapy and Experimental Therapeutics at Eshelman, told Contagion®. “Probably the reason is the 2 different compartments and how they’re primed to respond to estrogen.” Read more via Contagion

Title: Decreased tenofovir diphosphate concentrations in a transgender female cohort: Implications for HIV pre-exposure prophylaxis (PrEP)

Authors: Mackenzie L Cottrell, Heather MA Prince, Amanda P Schauer, Craig Sykes, Kaitlyn Maffuid, Amanda Poliseno, Tae-Wook Chun, Erin Huiting, Frank Z Stanczyk, Anne F Peery, Evan S Dellon, Jessica L Adams, Cindy Gay, Angela DM Kashuba

A meetings version of this work was presented at AIDS 2018. July 23-27, 2018, Amsterdam, Netherlands, Abstract TUPDX0106. Clinical Infectious Diseases

Abstract

Feminizing hormone therapy (FHT) may interact with HIV PrEP. We found transgender women taking FHT exhibited a 7-fold lower rectal tissue ratio of PrEP’s active metabolites vs competing deoxynucleotides compared to cisgender women and men (p=0.03) that inversely correlated with estradiol (ρ=-0.79; p<0.05). Thus FHT may negatively impact PrEP efficacy.