Hyperinflammatory Profiles and Early Mortality in HIV-Associated Tuberculosis: A Prospective Cohort Study in Brazil.

Abstract

Tuberculosis remains the leading cause of death among people with HIV, yet the immunological mechanisms underlying early mortality are incompletely defined. In this prospective cohort, 152 adults hospitalized with HIV-associated TB in Bahia, Brazil, had clinical/laboratory data and plasma cytokines measured at admission and day 7. Participants were followed for 100 days; deaths were classified as early (≤14 days) or late (15-100 days). We used clustering, canonical discriminant analysis, bootstrapped correlation networks, and multivariable logistic regression. Twenty-eight participants (18.4%) died: 13 early and 15 late. Early deaths had poorer functional status, greater organ dysfunction, less frequent early antiretroviral initiation, and biochemical evidence of intense systemic inflammation and coagulopathy. Unsupervised clustering did not clearly segregate outcomes, but early deaths displayed higher innate/chemotactic mediators and persistently dense, hyperconnected cytokine networks at baseline and day 7. Mortality was associated with higher day-7 TNF-α, IL-6 and GM-CSF and lower day-7 IL-2, as well as higher baseline IL-1ra and lower baseline TNF-β and IL-5; baseline International Normalized Ratio (INR) was the only biochemical predictor. Early mortality in this Brazilian cohort was characterized by a dysregulated, hyperconnected inflammatory state consistent with sepsis-like hyperinflammation, supporting immune-informed risk stratification and carefully designed host-directed studies.