# Improving PrEP protection of transgender women through mechanistic pharmacokinetic understanding

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $567,621

## Abstract

PROJECT SUMMARY
The goal of this work is to improve the medical care of transgender women (TGW) through understanding the
interaction of drugs for pre-exposure prophylaxis (PrEP) for prevention of HIV acquisition and gender affirming
hormonal therapy (GAHT). Professional Societies recommend estrogen-based GAHTs for TGW to promote
feminization and demasculinization in order to facilitate gender transition and diminish gender dysphoria. TGW
are a vulnerable population, who experience significant challenges, including gender dysphoria, depression,
and discrimination, all resulting in a compromised quality of life. There are barriers for transgender persons in
terms of employment and healthcare, further preventing members of the community from receiving culturally
competent care. In addition, TGW are 49-times at greater risk for HIV acquisition when compared to cisgender
men (CGM) and women (CGW) of reproductive age. Currently, a daily, fixed dose formulation of tenofovir
(TFV) disoproxil fumarate (TDF)/emtricitabine (FTC) (PrEP), has been used for the prevention of HIV
acquisition in persons at high risk of HIV infection. A less-frequent, on demand, four-dose regimen has also
proven highly effective in preventing HIV infection. While TGW have been enrolled in randomized controlled
PrEP trials, TGW have not been enrolled in sufficient numbers to robustly evaluate PrEP uptake and efficacy.
Importantly, the interaction of PrEP and GAHT drugs has not been well characterized. In vitro and ex vivo
studies suggest an influence of estrogen and, potentially reduced testosterone, on PrEP pharmacology.
Preliminary work by our group demonstrated greater than 30% reduction in plasma TFV and FTC AUC0-24 in
TGW on estrogen when compared to CGM. Because reducing the weekly TDF/FTC dose from seven to two
doses per week results in a sizeable drop in PrEP protection of anal sex from 90 to 75%, the change we
observed may be sufficiently large to impact PrEP outcomes in TGW on GAHT. Thus, to better characterize
the relationship between PrEP and GAHT, we propose a clinical drug-drug interaction between PrEP drugs
and estrogen-based GAHT in a stepwise and estrogen dose-dependent manner to quantify the magnitude of
drug interaction in blood, urine, and colorectal tissue. We will use these data, in conjunction with other clinical
trials data, to build a population pharmacokinetic-pharmacodynamic model of PrEP efficacy. This will enable
clinical trial simulations to contrast daily and on demand PrEP dosing in the presence and absence of GAHT to
inform PrEP dose recommendations for TGW. Because we hypothesize that GAHT will decrease PrEP
concentrations and result in increased susceptibility for HIV infection, TGW on GAHT will likely require higher
or more frequent PrEP dosing than CGM who have sex with men. This work is a critical next step in ensuring
appropriate PrEP dosing to group at substantially higher risk of HIV acquisition, and informs the need and
design for future ...

## Key facts

- **NIH application ID:** 10578778
- **Project number:** 5R01AI145675-05
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Mark A Marzinke
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $567,621
- **Award type:** 5
- **Project period:** 2019-03-11 → 2025-03-20

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10578778

## Citation

> US National Institutes of Health, RePORTER application 10578778, Improving PrEP protection of transgender women through mechanistic pharmacokinetic understanding (5R01AI145675-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10578778. Licensed CC0.

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