Contribution of Key Comorbidities to Unfavorable Treatment Outcomes Among Adults With Drug-Sensitive Pulmonary TB in India: A Prospective Cohort Analysis

Abstract

Background: The population-level impact of risk factors for unfavorable TB treatment outcomes depends on their relative prevalence in the population. Unadjusted and adjusted attributable fractions (AFs) were calculated to estimate the proportion of unfavorable TB treatment outcomes that can be attributed to key risk factors in India.

Research question: What proportion of unfavorable TB treatment outcomes can be attributed to key risk factors in India?

Study design and methods: Adults with drug-sensitive pulmonary TB were enrolled from 5 diverse clinical sites at treatment initiation and prospectively evaluated for 24 months. The primary outcome was a composite unfavorable treatment outcome of failure, recurrence, or death. Unadjusted and adjusted AFs were estimated for potentially modifiable risk factors of unfavorable treatment outcomes.

Results: A total of 2,930 adults contributed 32,912 person-months of follow-up. Median age was 43 years (interquartile range, 31-52 years), 2,136 (72.9%) participants were male, 1,609 (55.5%) were undernourished, 1,182 (40.4%) had ever smoked, 956 (32.8%) had diabetes, 437 (14.9%) reported alcohol misuse, and 65 (2.2%) were HIV positive. Overall, treatment failed in 129 participants, 80 had recurrence, and 101 died. In the unadjusted analysis, 32.2% (95% CI, 23.1-40.3) of all unfavorable outcomes were attributable to undernutrition, 19.4% (95% CI, 12.3-25.8) were attributable to ever-smoking, 8.5% (95% CI, 4.3-12.6) to alcohol misuse, and 1.6% (95% CI, 0.1-3.0) to HIV coinfection. After adjusting for simultaneous presence of multiple risk factors, 29.0% (95% CI, 17.6-38.8) of all unfavorable outcomes were found to be attributable to undernutrition. Alcohol misuse and ever-smoking accounted for 15.4% (95% CI, 7.9-22.3) and 17.9% (95% CI, 1.1-31.9) of treatment failures, respectively.

Interpretation: In this study, undernutrition, ever-smoking, and alcohol misuse accounted for more than one-third of all unfavorable treatment outcomes and may present high-yield intervention targets to improve TB treatment outcomes in India.

Keywords: HIV; TB; alcohol use disorder; attributable fractions; undernutrition.