Trial of oral fumagillin for the treatment of intestinal microsporidiosis in patients with HIV infection

Objective: Intestinal microsporidiosis caused by Enterocytozoon bieneusi is a cause of chronic diarrhoea in patients with HIV infection for which ther e is no current therapy. This study was designed to assess the safety and e fficacy of oral fumagillin in this infection. Design: A dose-escalation trial. Methods: Twenty-nine HIV-infected patients with E. bieneusi infection were consecutively enrolled in the trial. Oral doses of fumagillin were given to four groups of patients for 14 days: 10 mg/day (group 1), 20 mg/day (group 2), 40 mg/day (group 3), and 60 mg/day (group 4). Patients were seen at we eks 1, 2, 4 and 6 to assess safety and efficacy. Efficacy was assessed prim arily by the the clearance of microsporidia from stools and follow-up duode nal biopsies. Results: Thirteen patients complained of abdominal cramps, vomiting or diar rhoea during the study, and three patients had fumagillin withdrawn because of adverse events. Thrombocytopenia, neutropenia and hyperlipasaemia were the most frequent biological adverse events. Twenty-one out of 29 patients transiently cleared microsporidia from their stools during the study. By we ek 6, however, all patients in groups 1, 2 and 3 had parasitic relapse. Int erestingly, eight out of 11 (72%) patients treated with 60 mg/day (group 4) apparently cleared microsporidia from their gastrointestinal tract and gai ned weight. No parasitic relapse was documented in these eight patients dur ing a mean follow-up of 11.5 months. Conclusion: Treatment with fumagillin at 60 mg/day for 14 days has promise as an effective oral treatment for E, bieneusi infections, (C) 2000 Lippinc ott Williams & Wilkins.