Recombinant interferon-γ1b as adjunctive therapy for AIDS-related acute cryptococcal meningitis

We conducted a phase 2, double-blind, placebo-controlled study to evaluate the safety and antifungal activity of adjuvant recombinant interferon (rIFN)-gamma1b in patients with acquired immunodeficiency syndrome and acute cryptococcal meningitis. Patients received 100 or 200 mug of rIFN-gamma1b or placebo, thrice weekly for 10 weeks, plus standard therapy with intravenous amphotericin B, with or without flucytosine, followed by therapy with fluconazole. End points included conversion of cerebrospinal fluid fungal cultures from positive to negative at 2 weeks, resolution of symptoms, and survival. Among 75 patients, 2-week culture conversion occurred in 13% of placebo recipients, 36% of rIFN-gamma1b (100 mug) recipients, and 32% of rIFN-gamma1b (200 mug) recipients. There was a trend toward improved combined mycologic and clinical success in rIFN-gamma1b recipients (26% vs. 8%; P = .078). Therapy with rIFN-gamma1b was well tolerated, and there was no apparent influence on serial CD4 cell counts and human immunodeficiency virus load measurements. Adjunctive therapy with rIFN-gamma1b holds promise for patients with acute cryptococcal meningitis and warrants further study.