Genetic ancestry proportion influences risk of adverse events from tuberculosis treatment in Brazil

Tuberculosis (TB) treatment is highly effective, but response to therapy can vary by geography, race, and ethnicity. We assessed for differences in TB treatment response in a representative and heterogeneous Brazilian population. We estimated genetic ancestry proportion according to major ancestry groups (African, European, and Amerindian ancestry) in the Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil cohort. RePORT-Brazil is an observational prospective cohort study of individuals with newly-diagnosed, culture-confirmed, pulmonary TB. TB treatment outcomes that were attributed to TB treatment included Grade 2 or higher adverse drug reaction (ADR), Grade 3 or higher ADR, hepatic ADR, and failure/recurrence. Ancestry proportion was the main predictor in logistic regression for each outcome, with adjustments for candidate confounders. There were 941 pulmonary TB patients included in this study. We observed a decreased risk of Grade 2+ ADR when African ancestry proportion increased by 10% (Odds Ratio [OR] 0.41, 95% Confidence Interval [CI] 0.20 -0.85) and an increased risk for Grade 2+ ADR with increasing European ancestry (OR 2.84, 95% CI 1.47 - 5.48). We then performed the same analysis adding HIV status as an interaction term. The decreased risk for Grade 2+ ADR seen for African ancestry proportion did not hold for persons living with HIV; we observed increased risk for Grade 2+ ADR with increasing African ancestry proportion. There were no associations with Amerindian ancestry or for other treatment outcomes. In this Brazilian TB cohort, toxicity risk was associated with African and European ancestry, divergent, and affected by HIV.