This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This study will examine the effectiveness and safety of a combination treatment for cryptococcal meningitis, a fungal infection common in persons with acquired immune deficiency syndrome (AIDS) in the developing world. The standard initial treatment includes two medications: amphotericin B for 2 weeks followed by 8 weeks of fluconazole. This study will look at whether study participants recover more quickly and have fewer side effects if they are given both drugs at the same time for 2 weeks followed by 8 weeks of fluconazole as compared to the standard treatment. Participants will be followed for 6 months from the time they are enrolled into the study. Primary Obiective(s): 1. To assess the safety and tolerability of the study drug regimens. 2. 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 Objective(s): 1. To compare the efficacy of the study drug treatments at 2, 6, and 10 weeks (Days 14,42, and 70). 2. To compare the findings on detailed neurological examination between study arms at baseline and 2, 6, and 10 weeks, and 24 weeks (6 months). 3. To assess the proportion of subjects in each study arm that are alive at 6 months after initiation of study therapy. 4. To describe the effects of baseline clinical, neurological, and mycological characteristics on mycological failure at 2 and 10 weeks. 5. To measure time to CSF culture-negativity for each study arm. 6. To assess the length of hospitalization in the treatment groups as a surrogate of cost efficiency. 7. To assess the incidence of immune reconstitution inflammatory syndrome (IRIS) among all subjects receiving highly active antiretroviral therapy (HAART). 8. To examine antifunqal susceptibility of all clinical isolate
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