PDF(Pubmed)
Abstract：
The purpose of this systematic review is to provide updated evidence on the preferred induction therapy for the treatment of HIV-associated cryptococcal meningitis considering the most recent evidence available in order to inform the need for updates to WHO guidelines.
We searched Medline via PubMed, EMBASE, the Cochrane Library and clinicaltrials.gov for published or completed randomized clinical trials that evaluated induction treatment of first episode HIV-associated cryptococcal meningitis from 9 July 2018 (date of last search) to 1 September 2021.
One randomized clinical trial of 844 people with HIV-associated cryptococcal meningitis met the inclusion criteria. Participants were randomized to: (1) amphotericin deoxycholate for 7 days, with flucytosine and fluconazole (control); or (2) a single dose of liposomal amphotericin 10 mg/kg with flucytosine and fluconazole (intervention). In the intention-to-treat analysis, 10-week mortality was 24.8% [95% confidence interval (CI): 20.7-29.3%] in the single-dose liposomal amphotericin group compared with 28.7% (95% CI: 24.4-33.4%) in the control group. The absolute difference in 10-week mortality was -3.9% with an upper one-sided 95% CI of 1.2%, within the 10% pre-specified non-inferiority margin. Fewer participants had grade 3 and 4 adverse events in the intervention arm compared with the control arm (50.0% vs. 62.3%, p < 0.001).
In the single study included in this systematic review, single high-dose liposomal amphotericin B with flucytosine and fluconazole was non-inferior to the WHO-recommended standard of care induction therapy for HIV-associated cryptococcal meningitis, with significantly fewer adverse events.
We searched Medline via PubMed, EMBASE, the Cochrane Library and clinicaltrials.gov for published or completed randomized clinical trials that evaluated induction treatment of first episode HIV-associated cryptococcal meningitis from 9 July 2018 (date of last search) to 1 September 2021.
One randomized clinical trial of 844 people with HIV-associated cryptococcal meningitis met the inclusion criteria. Participants were randomized to: (1) amphotericin deoxycholate for 7 days, with flucytosine and fluconazole (control); or (2) a single dose of liposomal amphotericin 10 mg/kg with flucytosine and fluconazole (intervention). In the intention-to-treat analysis, 10-week mortality was 24.8% [95% confidence interval (CI): 20.7-29.3%] in the single-dose liposomal amphotericin group compared with 28.7% (95% CI: 24.4-33.4%) in the control group. The absolute difference in 10-week mortality was -3.9% with an upper one-sided 95% CI of 1.2%, within the 10% pre-specified non-inferiority margin. Fewer participants had grade 3 and 4 adverse events in the intervention arm compared with the control arm (50.0% vs. 62.3%, p < 0.001).
In the single study included in this systematic review, single high-dose liposomal amphotericin B with flucytosine and fluconazole was non-inferior to the WHO-recommended standard of care induction therapy for HIV-associated cryptococcal meningitis, with significantly fewer adverse events.
摘要：
背景：本系统评价的目的是考虑到现有的最新证据，提供关于治疗HIV相关隐球菌性脑膜炎的首选诱导疗法的最新证据，以告知需要更新WHO指南。
方法：我们通过PubMed搜索了Medline，EMBASE,Cochrane图书馆和clinicaltrials.gov的已发表或已完成的随机临床试验,这些试验评估了2018年7月9日(最后一次检索日期)至2021年9月1日首次HIV相关隐球菌性脑膜炎的诱导治疗.
结果：一项针对844名HIV相关性隐球菌性脑膜炎患者的随机临床试验符合纳入标准。参与者被随机分为：（1）两性霉素脱氧胆酸盐7天，与氟胞嘧啶和氟康唑（对照）;或（2）单剂量的脂质体两性霉素10mg/kg与氟胞嘧啶和氟康唑（干预）。在意向治疗分析中，单剂量脂质体两性霉素组的10周死亡率为24.8％[95％置信区间（CI）：20.7-29.3％]，而对照组为28.7％（95％CI：24.4-33.4％）。10周死亡率的绝对差异为-3.9％，上单侧95％CI为1.2％，在10%预先指定的非劣效性范围内。与对照组相比，干预组出现3级和4级不良事件的参与者较少(50.0%vs.62.3%,p<0.001)。
结论：在本系统评价中纳入的单个研究中，单次大剂量脂质体两性霉素B联合氟胞嘧啶和氟康唑不劣于WHO推荐的HIV相关隐球菌性脑膜炎的护理诱导治疗标准,显著减少不良事件。
方法：我们通过PubMed搜索了Medline，EMBASE,Cochrane图书馆和clinicaltrials.gov的已发表或已完成的随机临床试验,这些试验评估了2018年7月9日(最后一次检索日期)至2021年9月1日首次HIV相关隐球菌性脑膜炎的诱导治疗.
结果：一项针对844名HIV相关性隐球菌性脑膜炎患者的随机临床试验符合纳入标准。参与者被随机分为：（1）两性霉素脱氧胆酸盐7天，与氟胞嘧啶和氟康唑（对照）;或（2）单剂量的脂质体两性霉素10mg/kg与氟胞嘧啶和氟康唑（干预）。在意向治疗分析中，单剂量脂质体两性霉素组的10周死亡率为24.8％[95％置信区间（CI）：20.7-29.3％]，而对照组为28.7％（95％CI：24.4-33.4％）。10周死亡率的绝对差异为-3.9％，上单侧95％CI为1.2％，在10%预先指定的非劣效性范围内。与对照组相比，干预组出现3级和4级不良事件的参与者较少(50.0%vs.62.3%,p<0.001)。
结论：在本系统评价中纳入的单个研究中，单次大剂量脂质体两性霉素B联合氟胞嘧啶和氟康唑不劣于WHO推荐的HIV相关隐球菌性脑膜炎的护理诱导治疗标准,显著减少不良事件。
