A randomized, double‐blind, placebo‐controlled study of itraconazole capsules for the prevention of deep fungal infections in immunodeficient patients with HIV infection

Objectives  To determine whether systemic or deep fungal infections can be prevented, a double‐blind, placebo‐controlled, phase III trial of itraconazole prophylaxis was undertaken in HIV‐infected patients.Methods  HIV‐1 infected patients with CD4 counts < 300 cells/μL were treated with itraconazole (200 mg per day) or matching placebo and followed for 2 years. Development of deep fungal infections, episodes of mucocutaneous candidiasis, change in CD4 count, survival and safety data were collected at each study visit.Results  Three hundred and seventy‐four patients received study medication, 187 were given itraconazole and 187 matching placebo. Time to development of deep fungal infection did not differ between groups, in an intention to treat analysis. Low CD4 cell count and prior use of Pneumocystis carinii pneumonia (PCP) prophylaxis were significantly associated with a more rapid development of deep fungal infection (P = 0.044 and 0.017, respectively). Itraconazole treatment significantly reduced the incidence of oral candidosis (25% vs. 48% P < 0.001) and time to development of oral candidosis (508 vs. 413 days, P < 0.001) but not the number of deep fungal infections