ITRACONAZOLE TREATMENT OF DISSEMINATED HISTOPLASMOSIS IN PATIENTS WITH THE ACQUIRED-IMMUNODEFICIENCY-SYNDROME

PURPOSE: Amphotericin B has been the treatment of choice for dissemina ted histoplasmosis in patients with acquired immunodeficiency syndrome (AIDS). Oral antifungal agents would be welcome alternatives to stand ard treatment of disseminated histoplasmosis in less severe cases. The purpose of this study was to assess the efficacy and safety of itraco nazole therapy in patients with AIDS and disseminated histoplasmosis. PATIENTS AND METHODS: This was a multicenter, open-label, nonrandomize d prospective trial conducted in university hospitals of the AIDS Clin ical Trial Group. All patients had AIDS and first episodes of dissemin ated histoplasmosis. Patients with central nervous system involvement or with severe clinical manifestations were excluded. Patients were tr eated with itraconazole BID by mouth 300 mg for 3 days and then 200 mg BID for 12 weeks. Resolution of clinical findings, clearance of posit ive cultures, and drug tolerance were the main outcome measurements. A secondary objective was effect of therapy on Histoplasma capsulatum v ar capsulatum antigen levels. RESULTS: Of 59 evaluable patients, 50 (8 5%) responded to therapy. Five patients withdrew because of progressiv e infection, 1 died of a presumed pulmonary embolus within the first w eek of therapy without improvement, 2 withdrew because of toxicity, an d 1 was lost to follow-up after week 2 of therapy. Patients with moder ately severe clinical (fever >39.5 degrees C or Karnofsky score <60) o r laboratory abnormalities (alkaline phosphatase >5 times normal or al bumin <3 g/dL) at baseline tended to respond more poorly than did othe r patients. Resolution of complaints of fever and improvement in fatig ue occurred after a median of 3 and 6 weeks, respectively, and weight gain after 2 weeks. Fungemia cleared after a median of 1 week. H capsu latum var capsulatum antigen cleared from the urine and serum at rates of 0.2 and 0.3 units per week, respectively. CONCLUSIONS: Itraconazol e is safe and effective induction therapy for mild disseminated histop lasmosis in patients with AIDS, offering an alternative to amphoterici n B in such cases. Patients with moderately severe or severe histoplas mosis should first be treated with amphotericin B and then may be swit ched to itraconazole after achieving clinical improvement.