Antigen Clearance during Treatment of Disseminated Histoplasmosis with Itraconazole versus Fluconazole in Patients with AIDS

Antifungal treatment reduces the concentration of Histoplasma antigen in blood and urine, supporting a hypothesis that antigen clearance could be used to compare the activity of new agents for treating histoplasmosis. In separate trials in patients with AIDS, clinical response was similar with itraconazole (85%) and fluconazole (74%). Fungal blood cultures at week 4, however, were negative in a significantly higher proportion of patients treated with itraconazole (92.3%) than in those treated with fluconazole (61.9%) (P = 0.017). Baseline antigen concentrations were similar in the two groups: serum, P = 0.7235; and urine, P = 0.1360. After 4 weeks of treatment, the decline in antigen from baseline in serum was similar in the two treatment groups (P = 0.5237), as it was in urine (P = 0.4679). At week 12, the decline in antigen from baseline in serum also was similar in the two groups (P = 0.4911) and in urine (P = 0.2786). More rapid clearance of fungemia suggests that itraconazole is more effective than fluconazole in treating histoplasmosis. This study demonstrates that clearance of fungemia is a better measure of antifungal effect than clearance of antigen.