# Point-of-care pharmacogenomic testing to optimize isoniazid dosing for tuberculosis prevention

> **NIH NIH R21** · STANFORD UNIVERSITY · 2022 · $232,535

## Abstract

Project Summary
The discovery of effective antibiotic treatment and chemoprevention for tuberculosis was
among the most impactful scientific and public health advances in history. However, it is
increasingly clear that providing the same doses to all individuals leads to highly variable
drug concentrations, resulting in excess risk of toxicities and poor treatment outcomes.
For isoniazid, the most widely used drug for tuberculosis treatment and preventive
therapy, there is a high degree of interindividual variation in metabolism due to common
polymorphisms in the NAT2 gene. Individuals who have two NAT2 copies with mutations
conferring reduced activity (“slow acetylators”) are at increased risk of drug toxicities,
while individuals without mutations reducing activity (“rapid acetylators”), are at
increased risk of treatment failure, relapse, and acquired drug resistance. Major barriers
to implementing pharmacogenomic-guided dosing to address these problems have been
the lack of a diagnostic and lack of data on how to adjust isoniazid doses according to
acetylator genotype. We recently developed a cartridge-based, rapid molecular
diagnostic for the key NAT2 polymorphisms and an algorithm that accurately predicts
acetylator genotype. We propose to: 1) validate this assay in a diverse population in
Brazil using non-invasive samples, including fingerstick blood and oral swabs; and 2)
perform a Phase I clinical trial to determine whether pharmacogenomic-guided dose
modification among people receiving weekly isoniazid and rifapentine for preventive
therapy can reduce variation in drug levels. Overall, this project will generate
foundational data in the move towards personalizing tuberculosis treatment and
preventive therapy to reduce adverse events and improve outcomes for this disease of
global importance.

## Key facts

- **NIH application ID:** 10537650
- **Project number:** 1R21AI172182-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Jason Randolph Andrews
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $232,535
- **Award type:** 1
- **Project period:** 2022-09-23 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10537650

## Citation

> US National Institutes of Health, RePORTER application 10537650, Point-of-care pharmacogenomic testing to optimize isoniazid dosing for tuberculosis prevention (1R21AI172182-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10537650. Licensed CC0.

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