LIPOSOMAL AMPHOTERICIN-B (AMBISOME) COMPARED WITH AMPHOTERICIN-B BOTHFOLLOWED BY ORAL FLUCONAZOLE IN THE TREATMENT OF AIDS-ASSOCIATED CRYPTOCOCCAL MENINGITIS

Objective: Amphotericin B deoxycholate initial therapy and fluconazole maintenance therapy is the treatment of choice for AIDS-associated cr yptococcal meningitis. However, the administration of amphotericin B i s associated with considerable toxicity. A potential strategy for redu cing the toxicity and increasing the therapeutic index of amphotericin B is the use of lipid formulations of this drug. Design and methods: HIV-infected patients with cryptococcal meningitis were randomized to treatment with either liposomal amphotericin B (AmBisome) 4 mg/kg dail y or standard amphotericin B 0.7 mg/kg daily for 3 weeks, each followe d by fluconazole 400 mg daily for 7 weeks. During the first 3 weeks, c linical efficacy was assessed daily. Mycological response was primaril y evaluated by cerebrospinal fluid (CSF) cultures at days 7, 14, 21 an d 70. Results: Of the 28 evaluable patients, 15 were assigned to recei ve AmBisome and 13 to receive amphotericin B. Baseline characteristics were comparable. The time to and the rate of clinical response were t he same in both arms. AmBisome therapy resulted in a CSF culture conve rsion within 7 days in six out of 15 patients versus one out of 12 amp hotericin B-treated patients (P= 0.09), within 14 days in 10 out of 15 AmBisome patients versus one out of nine amphotericin B patients (P= 0.01), and within 21 days in 11 out of 15 AmBisome patients versus thr ee out of eight amphotericin B patients (P= 0.19). When Kaplan-Meier e stimates were used to compare time to CSF culture conversion, AmBisome was more effective (P< 0.05; median time between 7 and 14 days for Am Bisome versus > 21 days for amphotericin B). AmBisome was significantl y less nephrotoxic. Conclusions: A 3-week course of 4 mg/kg AmBisome r esulted in a significantly earlier CSF culture conversion than 0.7 mg/ kg amphotericin B, had equal clinical efficacy and was significantly l ess nephrotoxic when used for the treatment of primary episodes of AID S-associated cryptococcal meningitis.