title: Antigen clearance during treatment of disseminated histoplasmosis with itraconazole versus fluconazole in patients with AIDS.
abstract: 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.
authors.affiliation: Histoplasmosis Reference Laboratory, Indiana University School of Medicine and Veterans' Affairs Medical Center, Indianapolis, Indiana 46202-2879, USA. lwheat@iupui.edu
authors.forename: L Joseph
authors.initials: LJ
authors.lastname: Wheat
authors.forename: Patricia
authors.initials: P
authors.lastname: Connolly
authors.forename: Nicholas
authors.initials: N
authors.lastname: Haddad
authors.forename: Ann
authors.initials: A
authors.lastname: Le Monte
authors.forename: Edward
authors.initials: E
authors.lastname: Brizendine
authors.forename: Richard
authors.initials: R
authors.lastname: Hafner
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000378:metabolism / Q000635:transmission; D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000382:microbiology*; D000935:Antifungal Agents / Q000627:therapeutic use*; D000946:Antigens, Fungal / Q000032:analysis*; D015725:Fluconazole / Q000627:therapeutic use; D006660:Histoplasmosis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000635:transmission; D006801:Humans; D017964:Itraconazole / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D000946:Antigens, Fungal; D017964:Itraconazole; D015725:Fluconazole