# Feminizing Sex Hormones Impact on PrEP Pharmacology in Transgender Women

> **NIH NIH R21** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $156,630

## Abstract

PROJECT SUMMARY
Problem. Transgender women (TGW) have a 49-fold increased risk of becoming infected with HIV, yet they
have been underrepresented in HIV prevention and treatment research. Feminizing hormone therapy (FHT) can
alter the pharmacology of the nucleos(t)ide reverse transcriptase inhibitors (NRTIs) used for HIV pre-exposure
prophylaxis (PrEP) through complex physiologic mechanisms, but the clinical implication of this drug interaction
is unknown.
Our Overarching Goal: is to determine whether FHT diminishes PrEP's potency in TGW on FHT by decreasing
concentrations of the active metabolites (TFVdp/FTCtp) relative to their competing deoxynucleotides
(dATP/dCTP). We will use these data to construct a population PK model describing this ratio in HIV transmission
sites and predict PrEP efficacy in a transfeminine population taking and not taking FHT given different scenarios
of PrEP adherence and intermittent dosing.
Study Design: In Aim 1, we will conduct a study in 10 premenopausal women taking PrEP to determine how
high and low estradiol exposure impacts nucleotide concentrations in different cellular populations of the lower
gastrointestinal (GI) tract. We will measure TFVdp, FTCtp, dATP, and dCTP in total rectal cells collected by
cytobrush and CD4 cells isolated from tissue biopsies by LC-MS/MS. These data will be used to validate that
total rectal cells can be used as a pharmacology surrogate of isolated CD4+ T cells regardless of estradiol
exposure and to inform our sampling procedures for subsequent study. In Aim 2, we will leverage the San Diego
sites for a currently enrolling, multi-site PrEP demonstration project (PI Morris; NCT03086200) to co-enroll TGW
on PrEP taking and not taking FHT into our pharmacology study (N=10 each). We will collect blood (plasma,
serum, and peripheral blood mononuclear cells; PBMCs) as well as total rectal cells via anoscopy-assisted
cytobrush. We will measure sex hormones (estradiol, progesterone, and testosterone) in serum and TFVdp,
FTCtp, dATP, and dCTP in PBMC and total rectal cells by LC-MS/MS. In Aim 3 we will use these PK data to
build a population PK model of PrEP exposure in the lower GI tract and simulate PrEP exposure under different
dosing scenarios in 1000 TGW taking or not taking FHT. We will predict effectiveness of these simulations using
previously published PrEP efficacy targets.
Expected Outcomes: We believe these data will confirm our preliminary observations of ~7-fold decreased
concentrations in TFVdp relative to dATP in TGW taking FHT. Our population PK model to describe the impact
of FHT on PrEP pharmacology in HIV transmission sites will allow us to determine the minimal adherence
requirements to protect 99% of the transfeminine population taking FHT. These pharmacology data will support
an R01 application to explore dose taking and risk behavior and investigate PrEP outcomes in a cohort of TGW.

## Key facts

- **NIH application ID:** 9910363
- **Project number:** 5R21AI145646-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Mackenzie Cottrell
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $156,630
- **Award type:** 5
- **Project period:** 2019-04-09 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9910363

## Citation

> US National Institutes of Health, RePORTER application 9910363, Feminizing Sex Hormones Impact on PrEP Pharmacology in Transgender Women (5R21AI145646-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9910363. Licensed CC0.

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