A Randomized Clinical Trial of Immediate Versus Standard Antiretroviral Therapy for HIV-infected Adults Presenting With Cryptococcal Meningitis
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Change in the CSF CFUs between the immediate and standard ART initiation groups
研究概览
简要总结
The goal of this randomized clinical trial is to compare early versus standard timing of initiation of antiretroviral therapy (ART) with respect to clearance of Cryptococcus neoformans from cerebrospinal fluid (CSF) among HIV-infected adults with Cryptococcal Meningitis.
The investigators hypothesize that early ART mediates more rapid clearance of C. neoformans from CSF, as manifested by a greater rate of decrease in C. neoformans colony forming units (CFUs) during the first 28 days after initiating antifungal treatment.
Secondary hypotheses are that recovery of pathogen specific cellular immunity directed at C. neoformans, as manifested by increases in the number and function of C. neoformans-specific peripheral blood mononuclear cells is associated with 1) ART and 2) pathogen clearance. In addition, patients randomized to the intervention arm will have more rapid clearance of antigen levels in CSF and serum and will have a lower incidence of grade 3 and 4 Adverse events.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 21 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •HIV 1 infection confirmed by licensed ELISA kit and/or detectable Viral load.
- •Confirmed Cryptococcal meningitis on the current admission by India ink or CSF cryptococcal antigen
- •ART naive at the time of enrollment
- •21 years old and above
- •Ability and willingness to give written informed consent to participate in the study
- •Able (as assessed by the patient's medical team)to initiate amphotericin B for cryptococcal meningitis
- •Initiated amphotericin B 72 hours or less prior to assessment for enrollment or not on amphotericin B at the time of assessment for enrollment
- •Agrees to obtain outpatient care after discharge within 50 kilometers from Princess Marina Hospital,Scottish Livingstone Hospital and Bamalete Lutheran Hospital
排除标准
- •Recent (within the past 4 weeks) antifungal use
- •Pregnant or breastfeeding
- •Initiated anti-tubercular therapy 2 weeks or less prior to assessment for enrollment.
- •Bacterial meningitis at the time of assessment for enrollment.
- •Recent (within the past 1 month) use of the following:systemic cancer chemotherapy,oral or intravenous corticosteroids or other immunomodulators.
- •Judged by study coordinator to be likely to initiate chemotherapy or any other immunomodulatory therapy prior to the 4 week LP.
- •Imprisoned.
结局指标
主要结局
Change in the CSF CFUs between the immediate and standard ART initiation groups
时间窗: 4 weeks
次要结局
- Grade 3 or 4 adverse events(6 months)
- Clearance of C. neoformans antigen from CSF and blood.(6 months)
- Change in the number of peripheral blood mononuclear cells responding to C. neoformans(4 weeks)
研究者
Gregory Bisson
Assistant Professor of Medicine
Botswana-UPenn Partnership