A Phase II Randomized Trial of Amphotericin B Alone or Combined with Fluconazole in the Treatment

(See the editorial commentary by Harrison on pages 1784–6) Background. Cryptococcosis is a life-threatening infection among patients with human immunodeficientcy virus (HIV) infection. Therapeutic options for the treatment of central nervous system cryptococcosis are limited, especially in resource-limited settings. Methods. We conducted a randomized, open-label, phase II trial in Thailand and the United States that compared the safety and efficacy of intravenous amphotericin B deoxycholate (AmB) 0.7 mg/kg (the standard therapy) with that of AmB 0.7 mg/kg plus fluconazole 400 mg (the low-dosage combination) or AmB 0.7 mg/kg plus fluconazole 800 mg (the high-dosage combination) administered daily for 14 days, followed by fluconazole alone at the randomized dosage (400 or 800 mg per day) for 56 days. The primary safety end point was the number of severe or life-threatening treatment-related toxicities; the primary efficacy end point was a composite of survival, neurologic stability, and negative cerebrospinal fluid culture results after 14 days of therapy