# Short-course rifapentine for TB prevention for all: clinical  pharmacology matters

> **NIH NIH R37** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $843,516

## Abstract

PROJECT SUMMARY
Tuberculosis (TB) is the leading cause of death among people with HIV (PWHIV), and the risk of morbidity and
mortality is also high among young children and pregnant women. TB preventive therapy (TPT) to treat TB
infection (TBI) is especially important in these priority populations, but it must be safe and well-tolerated given
that TPT is largely provided to asymptomatic, healthy individuals. The Tuberculosis Trials Consortium (TBTC)
of the Centers for Disease Control and Prevention (CDC) is conducting ASTERoiD, a Phase 3 trial of rifamycin-
based TPT comparing six weeks of daily rifapentine (6wP) with local rifamycin-based standard of care (once-
weekly isoniazid and rifapentine for twelve weeks, 3HP; four months of daily rifampin (4R), or 3 months of daily
isoniazid and rifampin (3HR)). There are currently no pharmacokinetic (PK) assessments in ASTERoiD, and
optimal dosing of dolutegravir in PWHIV and rifapentine in priority populations in the context of 6wP has not
been firmly established. For this reason, PWHIV taking dolutegravir, children < 12 years, and pregnant women
are currently excluded from ASTERoiD We propose to enroll PWHIV taking DTG, children, and pregnant
people into a 6wP semi-intensive PK sub-cohort to confirm that model-informed doses of TB and HIV drugs
achieve target exposures in these participants (Aim 1). We will employ sparse PK sampling and use population
PK modeling to characterize exposure to rifapentine, explore sources of PK variability, and confirm that
translational modeling-informed dosing achieves clinical exposure targets in the majority of participants taking
6wP for TPT (Aim 2). We will evaluate TB drug exposures and pharmacogenetics as explanatory factors for
drug discontinuation due to adverse drug reactions, as well as other safety and tolerability outcomes, in both
the experimental and control arms in ASTERoiD (Aim 3). Finally, nesting clinical pharmacology into ASTERoiD
will provide us with the opportunity to understand whether or not key outcomes are related to drug exposures
and, importantly, will allow us to include key populations with the highest risk of TB disease and TB-related
morbidity and mortality into this Phase 3 trial of 6wP, an ultra-short, single-agent TPT that, if successful, could
transform TB prevention.

## Key facts

- **NIH application ID:** 11006936
- **Project number:** 1R37AI184117-01A1
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Kelly E. Dooley
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $843,516
- **Award type:** 1
- **Project period:** 2024-08-07 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11006936

## Citation

> US National Institutes of Health, RePORTER application 11006936, Short-course rifapentine for TB prevention for all: clinical  pharmacology matters (1R37AI184117-01A1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/11006936. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*