Histoplasmosis is a fungal infection caused by Histoplasma capsulatum, with greater severity in immunosuppressed patients, especially people with HIV/AIDS and CD4+ <150 cells/μL. This study aimed to evaluate clinical and laboratory predictors of probable disseminated histoplasmosis (DH) in patients with HIV infection in a hospital center in Northeastern Brazil.

Case-control study in Ceará, Brazil, from June 2023 to July 2024, using medical record review. Included were all patients who underwent lateral flow urine antigen testing for H. capsulatum (LF-AgHc Miravista®) per manufacturer instructions, with advanced AIDS (CD4+ <200 cells/μL or WHO clinical stage 3 or 4) or treatment interruption. The probable DH group included LF-AgHc-positive patients; controls were LF-AgHc-negative. The study was approved by the institutional ethics committee.

A total of 341 patients were analyzed; 41 in the DH group and 300 controls. Age, sex, and immune status were similar (p > 0.05). Fever >48h (70.7% vs. 41.3%; p = 0.002) and splenomegaly (17.1% vs. 5.6%; p = 0.007) were more frequent in DH. Dyspnea and hepatomegaly were similar between groups. Pancytopenia (36.6% vs. 8%), LDH >1000 U/L, and AST (TGO) >100 U/L were more frequent in DH (p < 0.001). Hospitalization occurred mainly in DH (92.7% vs. 68.7%; p < 0.001). Tuberculosis and other opportunistic infections were similar (p > 0.05). Among hospitalized patients (n = 244), death was more frequent in DH (23.7% vs. 8.7%; p = 0.024). In multivariable analysis, only LDH >1000 U/L remained a predictor of probable DH (OR 3.17; 95% CI 1.11–9.03).

Patients with advanced AIDS and elevated LDH should be tested using LF-AgHc. DH is an opportunistic infection with severe outcomes in people living with HIV/AIDS; these results reinforce the role of urine antigen testing for early detection in this population.