BAMSG 3-01

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。这项研究将检验一种联合治疗隐球菌脑膜炎的有效性和安全性。隐球菌脑膜炎是一种真菌感染，常见于发展中国家的获得性免疫缺陷综合征（艾滋病）患者。标准初始治疗包括两种药物：两性霉素B治疗2周，氟康唑治疗8周。与标准治疗相比，如果受试者同时服用两种药物2周，然后服用氟康唑8周，该研究将观察受试者是否恢复得更快，副作用是否更少。参与者将被跟踪6个月，从他们被纳入研究开始。主要目标：1；评估研究药物方案的安全性和耐受性。2. 确定联合治疗的安全性和有效性是否支持开展联合治疗的三期试验，如果支持，根据随后的三期试验评估的安全性和有效性，选择最合适的氟康唑加两性霉素B剂量。次要目标：1；比较研究药物治疗在第2、6和10周（第14、42和70天）的疗效。2. 比较两组患者在基线、2周、6周、10周和24周（6个月）时的详细神经学检查结果。3. 评估研究治疗开始后6个月存活的受试者比例。4. 描述基线临床、神经学和真菌学特征对2周和10周真菌学衰竭的影响。5. 测量各组脑脊液培养阴性的时间。6. 评估治疗组的住院时间作为成本效益的替代指标。7. 评估在所有接受高效抗逆转录病毒治疗（HAART）的受试者中免疫重建炎症综合征（IRIS）的发生率。8. 目的：检测所有临床分离株的抗真菌药敏

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