Predictors of mortality in individuals with disseminated histoplasmosis and advanced HIV disease

Disseminated histoplasmosis remains a major cause of morbidity and mortality among people living with advanced HIV disease (AHD), particularly in Latin America, where delayed diagnosis and limited access to optimal antifungal therapy persist. Accurate tools to assess disease severity and predict mortality are essential to guide clinical decision-making, including hospitalization, intensive care unit admission, and treatment strategies. We conducted a retrospective observational cohort study of hospitalized adults with AHD (CD4 ≤ 200 cells/mm³) and a first episode of probable or proven disseminated histoplasmosis at a tertiary referral center in São Paulo, Brazil, between 2013 and 2023. Disease severity at admission was assessed using four tools: the World Health Organization (WHO) severity classification, the Histoplasmosis Fatality Score (HFS), the Sequential Organ Failure Assessment (SOFA), and the quick SOFA (qSOFA). The primary outcome was in-hospital mortality. Eighty-nine individuals were included; most were male (77.5%), with a median age of 39 years and profound immunosuppression (median CD4 count 24 cells/mm³). In-hospital mortality was 34.8%. Individuals who died had significantly higher HFS and SOFA scores. In multivariable analysis, HFS, SOFA score, and serum creatinine were independently associated with in-hospital mortality, whereas qSOFA was not. HFS showed the best discriminatory performance (AUC 0.798; 95% CI 0.707-0.889). The combination of HFS and elevated creatinine further improved discrimination (AUC 0.840; 95% CI 0.758-0.922), outperforming the WHO classification, SOFA, and qSOFA in predicting in-hospital mortality. These findings support the use of HFS as a practical and reliable tool for stratifying disease severity, optimizing resource allocation, and guiding clinical decision-making in high-burden settings.