NAT2 rapid acetylator phenotype and increased risk of tuberculosis retreatment: A TB cohort study in Northern Thailand

Abstract

Objectives N-acetyltransferase 2 (NAT2) acetylator status affects circulating levels of isoniazid (INH). We investigated the association between NAT2 acetylator status and the rate of tuberculosis (TB) retreatment among patients who had previously completed treatment for drug-susceptible TB. Methods We analyzed patients aged ≥18 years with TB who completed standard treatment containing INH in Chiang Rai Province, Thailand (2017-2020). Hospital records were merged using Thailand's Health Data Center system to assess TB retreatment over two years. NAT2 acetylator status was determined from six single nucleotide polymorphisms. Cox proportional hazards models adjusted for age, sex, and ethnicity, with the risk period defined as 60-720 days post-treatment. Results Among 624 patients with tuberculosis in Thailand who completed therapy, 10% of the patients required retreatment within two years. NAT2 rapid acetylators exhibited a 2.00-fold (95% CI: 1.06-3.76) increased risk of retreatment compared with intermediate acetylators. Conclusion The association between NAT2 rapid acetylators and retreatment or treatment failure highlights the potential role of insufficient drug exposure with fixed-dose regimens.