CLINICAL AND IMMUNOLOGICAL FACTORS ASSOCIATED WITH MORTALITY IN HOSPITALIZED PATIENTS WITH TUBERCULOSIS AND HIV IN BRAZIL: A PROSPECTIVE COHORT STUDY

Tuberculosis (TB) remains the leading cause of death among people living with HIV (PLHIV). TB-HIV coinfection contributes substantially to global TB mortality. While previous studies have linked early mortality to delayed initiation of antiretroviral therapy (ART) and disseminated TB, the immunological mechanisms involved in these outcomes are still poorly understood, especially in endemic settings with high ethnic diversity such as Brazil. We conducted a prospective cohort study at Instituto Couto Maia (ICOM), a referral hospital for infectious diseases in Salvador, Bahia, between September 2023 and November 2024. We included adults with TB-HIV coinfection who had received up to seven doses of TB treatment at enrollment. Clinical, microbiological, and laboratory data were collected at admission and on day 7. Plasma cytokines were measured using Luminex technology. Mortality was assessed at 28 and 90 days, and participants were stratified into survivors, early deaths (≤14 days), and late deaths (15–90 days). Among 152 included patients, 28 (18.4%) died, with 13 early deaths and 15 deaths between days 15 and 90. Early mortality was associated with older age, lower Karnofsky performance status, and failure to initiate ART within the first seven days. There were no statistically significant differences between groups regarding sex, CD4 count, HIV viral load, or disseminated TB. Laboratory findings in early deaths showed a septic profile, with leukopenia, thrombocytopenia, hypoalbuminemia, and elevated D-dimer and procalcitonin levels. Immunologically, elevated and persistent inflammatory cytokines (IL-6, IL-8, TNF-α, G-CSF) and chemokines (IP-10) were observed, along with regulatory cytokines such as IL-10 and IL-1ra. Survivors showed a more controlled immune response and a significant decline in inflammatory biomarkers over time. Multivariable analyses confirmed the association between early mortality, exaggerated inflammation, low hemoglobin, and delayed ART initiation. In this study of hospitalized TB-HIV patients in Salvador, early mortality was associated with a dysregulated and persistent inflammatory response compatible with a septic phenotype.