Background In 2022, the World Health Organization (WHO) recommended a single 10 mg/kg dose of liposomal amphotericin B in combination with 14 days of flucytosine and fluconazole (AMBITION-cm regimen) for induction therapy of human immunodeficiency virus (HIV)-associated cryptococcal meningitis, based on the results of the multisite AMBITION-cm trial. We evaluated outcomes after real-world implementation of this novel regimen in Uganda. Methods We enrolled Ugandan adults with cryptococcal meningitis into an observational cohort receiving the AMBITION-cm regimen with therapeutic lumbar punctures in routine care during 2022–2023. We compared 10-week survival and CSF early fungicidal activity with the outcomes observed in the AMBITION-cm clinical trial conducted at the same sites. Results During 2022–2023, 179 adults were treated with the AMBITION-cm regimen via routine care and compared to the 171 adults randomized to the AMBITION-cm trial interventional arm in Uganda from 2018 to 2021. No significant difference in 10-week survival occurred between the observational cohort (68.6%; 95% confidence interval [CI]: 61.6%–76.3%) and AMBITION-cm trial participants in the intervention arm (71.7%; 95% CI: 65.2%–78.8%; absolute risk difference = −3.1%; 95% CI: −13.1% to 6.9%; P = .61). Early fungicidal activity did not differ (0.42 vs 0.39 log10CFU/mL/day; P = .80) between groups. Among observational cohort participants discharged alive initially and for whom follow-up data were available, the incidence of re-hospitalizations due to persistently elevated intracranial pressure was 2.8% (4/144). Conclusions The AMBITION-cm regimen for cryptococcal meningitis resulted in similar outcomes as observed in the AMBITION-cm clinical trial when implemented in routine care. Intracranial pressure management during hospitalization and awareness after discharge are key components of optimizing outcomes.

中文翻译：

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在乌干达实施基于脂质体两性霉素 B 的单一高剂量诱导治疗 HIV 相关隐球菌性脑膜炎：一项比较前瞻性队列研究


背景 2022 年，世界卫生组织 （WHO） 推荐单次 10 mg/kg 剂量的脂质体两性霉素 B 联合 14 天的氟胞嘧啶和氟康唑（AMBITION-cm 方案）用于人类免疫缺陷病毒 （HIV） 相关隐球菌性脑膜炎的诱导治疗，基于多中心 AMBITION-cm 试验的结果。我们评估了在乌干达实际实施这种新方案后的结局。方法 我们将患有隐球菌性脑膜炎的乌干达成年人纳入一个观察队列，该队列在 2022-2023 年期间接受 AMBITION-cm 方案和治疗性腰椎穿刺常规护理。我们将 10 周生存率和 CSF 早期杀真菌活性与在同一地点进行的 AMBITION-cm 临床试验中观察到的结果进行了比较。结果在 2022-2023 年期间，179 名成年人通过常规护理接受了 AMBITION-cm 方案治疗，并与 2018 年至 2021 年在乌干达随机分配到 AMBITION-cm 试验干预组的 171 名成年人进行了比较。观察队列 （68.6%;95% 置信区间 [CI]： 61.6%-76.3%） 和干预组 AMBITION-cm 试验参与者 （71.7%;95% CI： 65.2%-78.8%;绝对风险差 = -3.1%;95% CI： -13.1% 至 6.9%;P = .61）。早期杀真菌活性没有差异（0.42 vs 0.39 log10CFU/mL/天;P = .80） 组间。在最初活着出院且随访数据可用的观察队列参与者中，由于颅内压持续升高而再次住院的发生率为 2.8% （4/144）。结论 在常规护理中实施隐球菌性脑膜炎的 AMBITION-cm 方案导致与 AMBITION-cm 临床试验中观察到的相似结果。 住院期间的颅内压管理和出院后的意识是优化结果的关键组成部分。