Low-dose fluconazole as primary prophylaxis for cryptococcal infection in AIDS patients with CD4 cell counts of < or = 100/mm3: demonstration of efficacy in a positive, multicenter trial.

The efficacy of low-dose fluconazole (200 mg orally administered thrice weekly) as primary prophylaxis for cryptococcal infection was prospectively assessed in a multicenter trial involving 218 patients who were infected with human immunodeficiency virus (HIV) and who had CD4 cell counts of < or = 100/mm3. The median CD4 cell count at baseline was 39/mm3, 58% of the patients had an AIDS-defining illness or infection prior to enrollment. Cryptococcal meningitis occurred in 0.4% (1) of the 218 patients. The breakthrough isolate was susceptible to fluconazole, and the fluconazole kinetic study demonstrated adequate drug absorption and serum fluconazole levels; noncompliance could not be excluded in this case. Mucocutaneous and/or esophageal candidiasis developed in 18% (40) of the patients. Noncompliance with fluconazole therapy was the only variable independently associated with breakthrough candidiasis in the study patients (P = .00002). Thus, fluconazole (200 mg thrice weekly) given to HIV-infected patients with CD4 cell counts of < or = 100/mm3 was efficacious as primary prophylaxis for cryptococcosis, with notably lower costs and increased convenience for patients in comparison with daily administration of the drug.