• Safety-the number of dose-limiting toxicities attributed to treatment regimens. [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]
  
• Safety-examine the incidence of grade 3-5 adverse experiences that are definitely, probably, related to study drug. [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]
  

• All-cause mortality. [ Time Frame: 14, 42, and 70 days ] [ Designated as safety issue: No ]
  
• Incidence of immune reconsitution inflammatory syndrome (IRIS). [ Time Frame: 14, 42, and 70 days ] [ Designated as safety issue: No ]
  
• Length of hospitalization. [ Time Frame: 14, 42, and 70 days ] [ Designated as safety issue: No ]
  
• Key efficacy endpoint (treatment success) will be a composite of the 3 mycologic and clinical measures: CSF culture conversion; neurologically stable or improved; and alive. [ Time Frame: 14, 42, and 70 days ] [ Designated as safety issue: No ]
  
• Cerebrospinal fluid (CSF) culture conversion at multiple time points. [ Time Frame: 14, 42, and 70 days ] [ Designated as safety issue: No ]
  

This study is designed to address the need for more effective antifungal therapy for cryptococcal meningitis. This is a prospective, randomized, open-label, multicenter phase II clinical trial of combination therapy for the treatment of acute cryptococcal meningitis in HIV-positive subjects. The primary study objectives will be to assess the safety and tolerability of the study drug regimens; and to determine whether the safety and efficacy of combination therapy supports development of a phase III trial of combination therapy, and if so, to select the most appropriate dose of fluconazole plus amphotericin B based on safety and efficacy to be evaluated in a subsequent phase III trial. Secondary study objectives include: comparing the efficacy of the study drug treatments at 2, 6, and 10 weeks (Days 14, 42, and 70); comparing the findings on detailed neurological examination between study arms at baseline and 2, 6, 10, and 24 weeks (6 months); assessing the proportion of subjects in each study arm that are alive at 6 months after initiation of study therapy; describing the effects of baseline clinical, neurological, and mycological characteristics on mycological failure at 2 and 10 weeks; measuring time to cerebrospinal fluid (CSF) culture negatively for each study arm; assessing the length of hospitalization in the treatment groups as a surrogate of cost efficacy; assessing the incidence of immune reconstitution inflammatory syndrome among all subjects receiving highly active antiretroviral therapy (HAART); and examining antifungal susceptibility of all cryptococcal isolates. Study participants will include 150 subjects ages 13 and older. Subjects will be randomly assigned to 1 of 3 treatment arms including 1 standard therapy and 2 investigational arms. The standard treatment arm will include amphotericin B 0.7mg/kg (IV) for 14 days followed by 8 weeks (56 days) of fluconazole at 400mg/day orally. The 2 investigational arms will include daily amphotericin B 0.7mg/kg (IV) and the randomized dose of fluconazole 400mg/day or 800 mg/day for the first 14 day, then the randomized dose of fluconazole at 400mg/day or 800 mg/day respectively for an additional 8 weeks (56 days). At the completion of study therapy, all subjects will receive chronic suppressive therapy with oral fluconazole at a dose of at least 200 mg/day. The safety endpoints are considered to be the primary endpoints for this study. The safety assessment for each treatment arm will end at study day 100 for each subject. The key safety endpoint will be the incidence of adverse experiences of grade 3-5 (total and attributed to the treatment regimens). The primary safety endpoint will examine the incidence of grade 3-5 adverse experiences that are definitely or probably related to study drugs, while secondary analysis will include grade 3-5 adverse experiences that are definetly, probably or possibly related to study drugs. Another secondary safety endpoint will be the number of dose-limiting toxicities attributed to the treatment regimens. Key efficacy endpoint (treatment success) will be a composite of the following 3 mycologic and clinical measures after 14, 42, and 70 days of therapy: CSF culture conversion; neurologically stable or improved; and alive. Other secondary efficacy endpoints that will be evaluated descriptively are: CSF culture conversion at multiple time points; all-cause mortality; length of hospitalization; and incidence of immune reconstitution inflammatory syndrome.