Lack of Association Between Histoplasma Urine Antigen Values and Clinical Response in Persons without HIV

Background Histoplasma urine antigen detection, a valuable diagnostic tool, is often used to monitor response to antifungal therapy, but persistently positive antigen values, even when the infection has resolved, often present a clinical conundrum for clinicians. We sought to better define the course of urine antigen values in patients who do not have HIV and to evaluate whether changes correlate with resolution of infection. Methods Retrospective review of urine antigen tests and time to resolution of histoplasmosis for patients without HIV who were hospitalized between 1/1/15 and 2/1/24, and who had >2 sequential urine antigen tests performed. Results Twenty-seven patients were included: 24 (89%) had disseminated infection and 23 (85%) were immunocompromised. Antigen values were followed for as long as 39-58 months in some patients. Changes in antigen values over time roughly fell into 3 groups. For 7 patients the decrease in antigen corresponded with clinical response. Five patients, whose initial antigen levels were above the level of quantification of the assay, had persistence at this high level for up to 15 months after clinical response. For the remaining 15 patients, antigen slowly decreased, sometimes transiently increased, not mirroring the clinical response; four patients had persistent antigenuria for as long as 22 to 48 months after all symptoms, signs, and laboratory abnormalities had resolved. Conclusions These results support the concept that persistently positive Histoplasma urine antigen values, even very high levels, need not be the rationale for continued treatment in patients who have clinically responded and have completed recommended therapy.