TREATMENT OF HISTOPLASMOSIS WITH FLUCONAZOLE IN PATIENTS WITH ACQUIRED-IMMUNODEFICIENCY-SYNDROME

PURPOSE: This study assesses the efficacy and safety of fluconazole th erapy in patients with acquired immunodeficiency syndrome (AIDS) and m ild to moderately severe manifestations of disseminated histoplasmosis . PATIENTS AND METHODS: This was a multicenter, open-label, nonrandomi zed prospective trial. All patients had AIDS and disseminated histopla smosis. Patients were treated with 1,200 mg of fluconazole given by mo uth once on the first day, then 600 mg once daily for 8 weeks, and tho se patients who improved clinically were then assigned fluconazole mai ntenance therapy 200 mg once daily for at least 1 year. Interim analys is revealed a high failure rate (10 of 20, 50%), causing revision of t he protocol to increase the fluconazole dose to 1,600 mg given once on the first day, then 800 mg once daily, and the duration to 12 weeks f or induction therapy and then 400 mg daily for 1 year for maintenance therapy. MEASUREMENTS AND MAIN RESULTS: Thirty-six of 49 patients (74% ; 95% confidence interval [CI]: 59% to 85%) with mild to moderately se vere clinical manifestations who entered into the revised study respon ded to 800 mg of fluconazole daily for 12 weeks as induction therapy. Of the seven patients who failed induction therapy because of progress ion of histoplasmosis, one died of the infection. Of 36 patients who e ntered into the maintenance phase of the study receiving 400 mg of flu conazole daily for 1 year, 11 (30.5%) relapsed, including one who died (2.8%). Two of the 49 patients (4.1%) were removed because of grade 4 adverse events, alkaline phosphatase elevation for one and aspartate aminotransferase elevation in the other. The relapse-free rate at 1 ye ar was 53% (95% CI: 32% to 89%), prompting closure of the study. CONCL USIONS: Fluconazole 800 mg daily is a safe and moderately effective in duction therapy for mild or moderately severe disseminated histoplasmo sis in patients with AIDS. On the basis of historic comparison, flucon azole 400 mg daily is less effective than itraconazole 200 to 400 mg d aily or amphotericin B 50 mg given weekly as maintenance therapy to pr event relapse. (C) 1997 by Excerpta Medica, Inc.