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15 April 1993 | Volume 118 Issue 8 | Pages 610-616
Objective: To assess the efficacy and safety of itraconazole in preventing relapse of histoplasmosis after induction therapy with amphotericin B in patients with the acquired immunodeficiency syndrome (AIDS) and disseminated histoplasmosis.
Design: A prospective, multicenter, open-label clinical trial, with follow-up for at least 52 weeks.
Setting: Tertiary care hospitals participating in a clinical investigation sponsored by the National Institutes of Allergy and Infectious Diseases (AIDS Clinical Trial Group and Mycoses Study Group).
Patients: Forty-two patients with AIDS who had successfully completed induction therapy for disseminated histoplasmosis amphotericin B, at least 15 mg/kg body weight given over 4 to 12 weeks.
Interventions: Itraconazole, 200 mg given orally twice daily.
Main Outcome Measures: Response to therapy, specifically prevention of histoplasmosis relapse, was the main outcome measure. Secondary end points were survival and the effect of therapy on Histoplasma capsulatum variety capsulatum antigen levels in urine and serum. Plasma itraconazole concentrations were measured to document drug absorption and compliance with therapy.
Results: The median follow-up was 109 weeks, and median survival was 98 weeks. Two relapses occurred (5%; 95% CI, 0.5% to 16%), one in a patient withdrawn from the study 18 weeks earlier and one in a patient who did not comply with the study therapy. Patients with elevated antigen levels at study entry showed clearance of antigen from urine and serum; urine specimens became negative in 43% of patients (CI, 26% to 59%), and serum specimens became negative in 75% of patients (CI, 56% to 94%). Only one patient discontinued treatment because of itraconazole toxicity (hypokalemia).
Conclusions: Itraconazole, 200 mg twice daily, is safe and effective in preventing relapse of disseminated histoplasmosis in patients with AIDS. Antigen clearance from blood and urine correlates with clinical efficacy.
* For a list of other contributors to the study, see end the Appendix.
Author and Article Information
From Indiana University School of Medicine and Richard L. Roudebush Veterans Affairs Hospital, Indianapolis, Indiana; National Institutes of Health, Bethesda, Maryland; Harvard School of Public Health, Newton, Massachusetts; Cornell University, New York, New York; Washington University, St. Louis, Missouri; University of Cincinnati College of Medicine, Cincinnati, Ohio; University of Texas Health Science Center, San Antonio, Texas; Department of Veterans Affairs Medical Center, Birmingham, Alabama; Department of Veterans Affairs Medical Center, Houston, Texas; Northwestern University Medical School, Chicago, Illinois; Frontier Science and Technical Research Foundation, Amherst, New York.
ARTICLE
Prevention of Relapse of Histoplasmosis with Itraconazole in Patients with the Acquired Immunodeficiency Syndrome
Requests for Reprints: Joseph Wheat, MD, Indiana University School of Medicine, Wishard Memorial Hospital, Room OPW430, 1001 West Tenth Street, Indianapolis, IN 46202-2879.
Grant Support: In part by the Division of AIDS of the National Institutes of Allergy and Infectious Diseases; National Institutes of Allergy and Infectious Diseases Mycoses Study Group contract 1-AI-15082; and the Department of Veterans Affairs.
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