Genetic ancestry proportion influences risk of adverse events from tuberculosis treatment in Brazil
Year: 2026
Type: article
Abstract: 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. #RePORT-Brazil Consortium members include: Aline Benjamin and Flavia M. Sant'Anna Instituto Nacional de Infectologia Evandro Chagas, Fiocruz, Rio de Janeiro, Brazil Jamile Garcia de Oliveira and João Marine Clínica de Saúde Rinaldo Delmare, Rio de Janeiro, Brazil Adriana Rezende and Anna Cristina Carvalho Secretaria de Saúde de Duque de Caxias, Rio de Janeiro, Brazil Michael Rocha and Betânia Nogueira Instituto Brasileiro para Investigação da Tuberculose, Fundação José Silveira, Salvador, Brazil Alexandra Brito and Renata Spener Fundação Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil Megan Turner Vanderbilt University Medical Center, Nashville, USA.
Source: Human Genetics
Authors: Jacqueline A. Piekos, Gustavo Amorim, Felipe Ridolfi, Marcelo Cordeiro-Santos, Afrânio L. Kritski, Marina C. Figueiredo, Bruno B. Andrade, Adalberto R. Santos, David W. Haas, Timothy R. Sterling, Valeria C. Rolla, Digna R. Velez Edwards, Aline Benjamin, Flavia M. Sant’Anna, Solange Cavalcante, Betina Durovni, Jamile Garcia de Oliveira, João Marine, Adriana Rezende, Anna Cristina Carvalho, Michael Rocha, Betânia Nogueira, Alexandra Brito, Renata Spener, Megan Turner, James Jaworski
Institutions: Vanderbilt University, Vanderbilt University Medical Center, Fundação Oswaldo Cruz, Fundação de Medicina Tropical, Universidade do Estado do Amazonas, Universidade Federal do Rio de Janeiro, Escola Bahiana de Medicina e Saúde Pública, Faculdade de Tecnologia e Ciências, Universidade Salvador, Meharry Medical College
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,690
Awards: Predictors of treatment toxicity, failure, and relapse in HIV-related tuberculosis, G3441327761, G5452137875, G6488665543, G768658969, The Vanderbilt Institute for Clinical and Translational Research (VICTR), G862854160, G9000033427, G9000048758, Tennessee Center for AIDS Research (TN-CFAR), G9000177955, G9000313355, G9000344391, Regional Prospective Observational Research in Tuberculosis (RePORT) – Brazil Network, Caribbean, Central, and South America network for HIV Epidemiology (CCASAnet)
OpenAlex ID: W7119031654