背景:隐球菌性脑膜炎是艾滋病相关死亡的主要原因。隐球菌抗原(CrAg)可预测脑膜炎的发展。历史上,尽管有治疗标准的氟康唑,25%-30%的无症状CrAg阳性患者发展为突破性脑膜炎或死亡。我们评估了在标准抢先氟康唑治疗中添加单次高剂量两性霉素B脂质体是否可以改善无脑膜炎生存率。
方法:乌干达患有人类免疫缺陷病毒(HIV)和无症状隐球菌抗原血症的参与者被随机分配至脂质体两性霉素B(10mg/kg,一次)与氟康唑或氟康唑单独治疗24周。我们比较了24周,治疗组之间无脑膜炎生存时间。第二次中期审查后,数据安全和监测委员会建议,由于无效,不进一步纳入血浆CrAg侧流测定滴度低(≤1:80)的参与者.在这里,我们提出了低血浆CrAg滴度的参与者的结果。
结果:参加ACACIA试验的168名参与者血浆CrAg滴度较低(≤1:80)。在24周的随访中,脑膜炎或死亡发生在14.5%(12/83)的随机接受脂质体两性霉素B联合氟康唑的参与者中,与10.6%(9/85)的单独接受氟康唑的参与者相比(风险比,1.42;95%CI,.60-3.36;P=.431)。与标准护理相比,接受干预的参与者的不良事件发生率更高(28%vs12%;P=.011)。
结论:在低滴度(≤1:80)的CrAg阳性人群中,在氟康唑中加入单剂量两性霉素B脂质体作为先发制人疗法,没有带来额外的临床获益.该试验提供了支持性证据,在血浆CrAg滴度低的无症状人群中,腰椎穿刺可能是不必要的,因为给予脑膜炎治疗并不能改善结局.
背景:Clinicaltrials.gov(NCT03945448)。
BACKGROUND: Cryptococcal meningitis is a leading cause of AIDS-related mortality. Cryptococcal antigen (CrAg) predicts the development of meningitis. Historically, despite standard- of-care fluconazole, 25%-30% of asymptomatic CrAg-positive persons develop breakthrough meningitis or death. We evaluated whether adding single high-dose liposomal amphotericin B to standard pre-emptive fluconazole therapy could improve meningitis-free survival.
METHODS: Participants with human immunodeficiency virus (HIV) and asymptomatic cryptococcal antigenemia in Uganda were randomized to liposomal amphotericin B (10 mg/kg once) with fluconazole or fluconazole alone through 24 weeks. We compared 24-week, meningitis-free survival time between treatment groups. After the second interim review, the Data Safety and Monitoring Board recommended no further enrollment of participants with low plasma CrAg lateral flow assay titers (≤1:80) due to futility. Herein, we present the results of participants with low plasma CrAg titers.
RESULTS: 168 participants enrolled into the ACACIA trial had low plasma CrAg titers (≤1:80). During 24 weeks of follow-up, meningitis or death occurred in 14.5% (12/83) of participants randomized to liposomal amphotericin B with fluconazole versus 10.6% (9/85) assigned to fluconazole alone (hazard ratio, 1.42; 95% CI, .60-3.36; P = .431). Adverse events were more frequent in participants assigned to the intervention versus standard-of-care (28% vs 12%; P = .011).
CONCLUSIONS: Among CrAg-positive persons with low titers (≤1:80), the addition of single-dose liposomal amphotericin B to fluconazole as pre-emptive therapy provided no additional clinical benefit. This trial provides supportive evidence that, in asymptomatic populations with low plasma CrAg titers, lumbar punctures are likely unnecessary as administration of meningitis treatment did not improve outcomes.
BACKGROUND: Clinicaltrials.gov (NCT03945448).