Host factors, not Mycobacterium tuberculosis lineage, predict unfavorable outcomes in drug-susceptible pulmonary tuberculosis: evidence from RePORT-Brazil

To determine whether Mycobacterium tuberculosis (Mtb) lineage was independently associated with clinical presentation and unfavorable treatment outcomes in drug-susceptible pulmonary tuberculosis (TB) in a large Brazilian cohort. We analyzed 900 rifampicin- and isoniazid-susceptible Mtb isolates from adults enrolled in the multicenter RePORT-Brazil cohort using 24-loci MIRU-VNTR genotyping. Treatment outcome analyses included 772 participants with complete follow-up. Associations between lineage and a composite unfavorable outcome (death, failure, or recurrence) were evaluated using pre-specified multivariable Firth logistic regression adjusted for demographic, clinical, and geographic factors. Thirteen lineages were identified, predominantly LAM (56.7%) and Haarlem (30.6%). Although lineage distribution varied by region, lineage was not independently associated with unfavorable outcomes. HIV infection and older age were the strongest predictors. Baseline clinical features and treatment outcomes were largely similar across lineages. Among 43 participants with positive month-2 cultures, 22 were genotyped and in 5/22 (22.7%) the month-2 isolate belonged to a different lineage from the baseline isolate, consistent with reinfection or mixed infection. In drug-susceptible pulmonary TB, host-related factors, rather than Mtb lineage, were more strongly associated with unfavorable treatment outcomes.