PREVENTION OF RELAPSE OF HISTOPLASMOSIS WITH FLUCONAZOLE IN PATIENTS WITH THE ACQUIRED-IMMUNODEFICIENCY-SYNDROME

OBJECTIVE: TO assess the effectiveness of fluconazole for suppression of relapse of histoplasmosis in patients with acquired immunodeficienc y syndrome (AIDS). DESIGN: Retrospective, nonrandomized, open trial. S ETTING: Multicenter at two university referral centers and in five pri vate practices. PATIENTS: Seventy-six patients with AIDS and dissemina ted histoplasmosis who completed induction treatment with amphotericin B, itraconazole, or fluconazole and maintained on treatment with fluc onazole to prevent relapse. INTERVENTIONS: Fluconazole was given at do sages of 100 to 400 mg per day. Patients were followed by their primar y physicians, who completed questionnaires collecting information abou t treatment and relapse status. Blood and urine specimens were submitt ed periodically for Histoplasma capsulatum var, capsulatum antigen det ermination. MEASUREMENTS AND MAIN RESULTS: Nine of the 76 patients rel apsed during fluconazole therapy and another was removed from the stud y because of allergic rash. Survival after initiation of therapy for h istoplasmosis was 94 weeks, ranging from 74 weeks for those who receiv ed less than 1 g of amphotericin B for induction and none for maintena nce therapy to 156 weeks for those who received greater than 1 g for i nduction and additional amphotericin B for maintenance therapy before beginning fluconazole (P <0.02). Antigen levels fell at rates of 0.05 units/week in urine and 0.02 units/week in serum in patients who were successfully maintained in remission and increased by greater than or equal to 2 units/week in 4 of 6 patients who relapsed. CONCLUSIONS: Fl uconazole greater than or equal to 200 mg daily is a reasonable choice for chronic suppressive therapy of histoplasmosis in patients who can not take itraconazole because of drug interactions, malabsorption, or side effects.