A controlled trial of itraconazole to prevent relapse of Penicillium marneffei infection in patients infected with the human immunodeficiency virus

Background In Southeast Asia, disseminated infection with Penicillium marneffei is common among patients with human immunodeficiency virus (HIV) infection. Even after successful primary treatment, the relapse rate for this potentially fatal systemic fungal infection is about 50 percent. Methods We conducted a double-blind trial in Thailand to evaluate itraconazole as secondary prophylaxis against P. marneffei infection in patients with the acquired immunodeficiency syndrome (AIDS) who were in complete remission after treatment for culture-proved P. marneffei infection. The patients were randomly assigned to receive either oral itraconazole (200 mg daily) or placebo as maintenance therapy. Results Of the 72 HIV-infected patients who completed initial treatment for P. marneffei infection, 71 were enrolled in the maintenance study. None of the 36 patients assigned to itraconazole had a relapse of P. marneffei infection within one year, whereas 20 of the 35 patients assigned to placebo (57 percent) had relapses (P<0.001). Among the 20 patients who had relapses, P, marneffei was cultured from blood (15 patients), lymph-node tissue (3 patients), skin (3 patients), and sputum (1 patient). The median time to relapse was 24 weeks after the completion of the initial treatment (95 percent confidence interval, 19.0 to 36,1). Survival and toxic effects were similar in the two groups. Conclusions In patients infected with HIV who have completed successful primary treatment of FI marneffei infection, secondary prophylaxis with oral itraconazole is well tolerated and prevents relapses of this opportunistic infection. (N Engl J Med 1998;339:1739-43.) (C) 1998, Massachusetts Medical Society.