Histoplasma Capsulatum Antigen Persistence and Rate of Decay During Treatment of Histoplasmosis Varies by Immune Status.

BACKGROUND: Previous studies examining Histoplasma antigen trends are largely in people living with HIV (PLWH) before the antiretroviral therapy era, with limited generalizability to modern cohorts of histoplasmosis. METHODS: We conducted a single-center, retrospective study of adult patients diagnosed with histoplasmosis by positive antigen testing and undergoing treatment between 2007 to 2021. Mean rates of antigen clearance were estimated using a linear mixed effects model. Time to H. capsulatum antigen negativity was calculated using competing risk analysis. Per-patient, mean antigen levels were compared at time of diagnosis and subsequent 6mo intervals. RESULTS: 83 patients met inclusion criteria: 25 transplant, 21 immunocompetent, 16 biologic therapy, 11 PLWH, and 10 with other immunocompromise (OI). The transplant (-0.07), biologic (-0.07), and OI groups (-0.05) cleared antigenuria significantly slower than PLWH (-0.21) and the immunocompetent group (-0.16). Median time to antigen negativity in the presence of competing risk of death was transplant: 20.3 months (95% CI: 11.6, 69.3), biologic: 14.6 months (9.0, 42.6), OI: 13.2 months (2.0, 82.5), PLWH: 12.9 months (1.9, 19.2), and immunocompetent: 6.8 months (2.8, 13.0). At one year, antigen positivity was more common in immunocompromised than immunocompetent patients (22/40, 55% vs. 3/16, 19%; p = 0.02) and among the immunocompromised groups only transplant, biologic, and OI patients had positivity at two years. CONCLUSIONS: Patients with chronic non-HIV immunosuppression demonstrated persistent antigenuria and cleared antigen more slowly compared to immunocompetent patients and immune reconstituted PLWH. Given the association of antigen persistence with immune status, its clinical significance in non-HIV immunocompromised populations requires evaluation.