One-year mortality of tuberculosis patients on isoniazid-based treatment and its association with rapid acetylator NAT2 genotypes

Background NAT2 polymorphisms affect isoniazid metabolism, but their effect on mortality among individuals with tuberculosis (TB) remains unclear. Methods This study used data from two TB cohorts (2005-2011, 2014-2020) and death certificate records in Thailand. Newly diagnosed Thai individuals treated with isoniazid-containing regimens were included. NAT2 genotypes-rapid, intermediate, and slow acetylator (RA, IA, SA)-were classified via haplotype inference. The primary outcome was 1-year all-cause mortality, while secondary outcomes included TB-related mortality, TB+respiratory disease-related mortality recorded in the vital registration system, and death as a TB treatment outcome. Adjusted hazard ratios (aHRs) relative to the IA type were estimated using stratified Cox proportional hazards models. Subgroup analyses targeted individuals with isoniazid-resistant TB and HIV infection. Results A total of 1,065 individuals (766 males; mean age=51 years) were analyzed. Individuals with RA had a 1.70-fold greater all-cause mortality risk (95 % CI: 1.03-2.80) than IA. The aHRs for RA were 1.14 (0.43-3.03) for TB-related mortality, 1.59 (0.80-3.18) for TB+respiratory disease-related mortality, and 1.26 (0.67-2.37) for TB treatment outcome death. Among individuals with isoniazid-resistant TB, those with RA had a 4.68-fold (1.14-19.12) greater aHR for all-cause mortality. Conclusion The RA type is associated with increased 1-year all-cause mortality.