The prep optimization in women via event-driven regimens (POWER) study

The National Institute of Allergy and Infectious Diseases awarded The Johns Hopkins University $691,288 on July 6, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to conduct the PREP Optimization in Women via Event-Driven Regimens (POWER) study, a pharmacokinetic and pharmacodynamic investigation of emtricitabine/tenofovir disoproxil fumarate (F/TDF) pre-exposure prophylaxis in women receiving exogenous hormone therapy.

The study quantifies F/TDF drug concentrations at mucosal sites of sexual exposure—the female genital tract and rectum—to assess event-driven or on-demand ("2-1-1") F/TDF dosing efficacy in women and to characterize testosterone-mediated differences in F/TDF pharmacologic parameters and cervicovaginal immune responses that may affect HIV prevention protection. The research addresses knowledge gaps in F/TDF pharmacokinetics and pharmacodynamics across anatomic sites of HIV transmission in women on therapeutic testosterone, a population where limited pharmacologic data exists and conflicting evidence surrounds the viability of less-than-daily PREP dosing.

Work is performed in Baltimore, Maryland, with a period of performance through June 30, 2031. The Johns Hopkins University co-leads the multidisciplinary team as the parent grantee with co-investigator Mark Marzinke serving as the co-principal investigator.

Two sub-recipients support the award. Medstar Health Research Institute Inc., under a sub-award dated September 1, 2026, provides multidisciplinary team leadership through co-principal investigator Dr. Scott, oversight of participant enrollment and biospecimen collection, and annual community advisory board convening. The Research Foundation for the State University of New York, under a sub-award dated August 28, 2026, develops pharmacokinetic and pharmacodynamic models extending current F/TDF models to include rectal and vaginal compartments, with collaboration across Georgetown University, George Washington University, and Johns Hopkins.

Abstract

Women shoulder the burden of the global HIV pandemic, comprising 53% of the nearly 40 million people living with HIV worldwide. Understanding HIV prevention among women on exogenous hormone therapy, such as therapeutic testosterone, is key to HIV prevention among women. While oral emtricitabine/tenofovir disoproxil fumarate (F/TDF) is the most widely available form of biomedical HIV pre-exposure prophylaxis (PREP), IT remains underutilized among women. Testosterone has been shown to modulate mucosal immune responses in the female genital tract, and the implications of these changes on cervicovaginal immunity, HIV risk enhancement, and F/TDF-mediated protective efficacy are unknown. Recommended dosing of F/TDF for PREP in women is limited to daily oral dosing; there are conflicting data and significant knowledge gaps in the viability of event-driven or on-demand ("2-1-1") F/TDF PREP efficacy in women. Quantification of PREP concentrations at the sites of sexual exposure (i.e., mucosa of the rectum and female genital tract) is key to understanding F/TDF PREP prevention efficacy, particularly with less than daily dosing. As such, we hypothesize there will be testosterone-mediated differences in F/TDF pharmacologic parameters in the female genital tract in women, and PREP concentrations in the female genital tract will not confer protection from HIV acquisition among women on therapeutic testosterone. Based on the sparseness of pharmacologic data in the female genital tract for event-driven PREP and the unknown consequences of testosterone-mediated changes in cervicovaginal immunomodulatory markers on F/TDF pharmacokinetics (PK) and pharmacodynamics (PD) (e.g., HIV susceptibility), significant knowledge gaps exist in our understanding of the relationship between exogenous and endogenous hormones and F/TDF in anatomic sites of HIV viral transmission. Our aims address the above gaps through a PK/PD study of oral daily and event-driven (2-1-1) PREP regimens in women not on hormone therapy and women on therapeutic testosterone: aim 1. Characterization of the pharmacologic relationship between F/TDF and therapeutic-dose testosterone in the female genital tract and rectum. Aim 2. Interrogation of F/TDF pharmacologic differences in the female genital tract and rectal mucosa between daily oral F/TDF and event-driven F/TDF. Aim 3: F/TDF population PK analysis and simulations to refine current models and to evaluate the contribution of therapeutic-dose testosterone in the rectal mucosa and female genital tract.