Rates and Risk Factors for On‐Treatment Mortality Among a Cohort of Adults Treated for Drug‐Sensitive Tuberculosis: Analysis of Data From the Adherence Support Coalition to End Tuberculosis Consortium in Five Countries

BACKGROUND: Tuberculosis remains a leading cause of death globally, particularly in countries with high tuberculosis and HIV burdens. Disruptions caused by the COVID-19 pandemic may have further impacted tuberculosis outcomes. This study examines on-treatment mortality and associated risk factors in five countries. METHOD: We conducted a secondary analysis of data from ASCENT cluster-randomised trials of digital adherence tools for improved adherence involving 23,799 adults with drug-sensitive tuberculosis in South Africa, Tanzania, Ethiopia, the Philippines, and Ukraine. Analyses were conducted separately by country. Mortality rates were measured from treatment initiation to the earliest of 6 months, death, or loss to follow-up. Cox regression models (with random effects or robust standard errors for clustering) assessed the associations between mortality and HIV status, ART use, tuberculosis diagnosis type, and calendar periods (COVID-19 pandemic and conflict in Ukraine). RESULTS: Mortality rates ranged from 7.6 (Ethiopia) to 23.2 (Tanzania) and 23.3 (Ukraine) per 100 person-years. Higher mortality was associated with: older age in all countries (age < 30 versus ≥ 60 years, adjusted rate ratio [aRR] ranging from 2.38 to 6.57 by country); HIV status (positive versus negative, aRR ranging from 1.44 to 2.98 by country); tuberculosis diagnosis type (clinical vs. bacteriological, aRR 1.5-1.6 in Ethiopia, Tanzania and South Africa); extrapulmonary tuberculosis (aRR 1.44 to 1.60 in Ukraine and Tanzania). ART versus HIV-positive not on ART was linked to lower mortality in South Africa and Ukraine but not in Tanzania. Analyses suggested possible mortality variations by calendar period. CONCLUSION: Our findings suggest variability in tuberculosis mortality across settings, influenced by HIV/ART and diagnosis type. The high mortality rates across countries may reflect underlying causes or potential misdiagnoses. Further investigation into these factors may be needed to improve tuberculosis outcomes globally.