Department of Infectious Diseases, Cambridge University Hospitals National Health Service Foundation Trust, Cambridge, United Kingdom.
Clin Infect Dis. 2011 Jun;52(11):1374-83. doi: 10.1093/cid/cir230.
The optimal time to initiate antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-associated tuberculous meningitis is unknown.
We conducted a randomized, double-blind, placebo-controlled trial of immediate versus deferred ART in patients with HIV-associated tuberculous meningitis to determine whether immediate ART reduced the risk of death. Antiretroviral drugs (zidovudine, lamivudine, and efavirenz) were started either at study entry or 2 months after randomization. All patients were treated with standard antituberculosis treatment, adjunctive dexamethasone, and prophylactic co-trimoxazole and were followed up for 12 months. We conducted intention-to-treat, per-protocol, and prespecified subgroup analyses.
A total of 253 patients were randomized, 127 in the immediate ART group and 126 in the deferred ART group; 76 and 70 patients died within 9 months in the immediate and deferred ART groups, respectively. Immediate ART was not significantly associated with 9-month mortality (hazard ratio [HR], 1.12; 95% confidence interval [CI], .81-1.55; P = .50) or the time to new AIDS events or death (HR, 1.16; 95% CI, .87-1.55; P = .31). The percentage of patients with severe (grade 3 or 4) adverse events was high in both arms (90% in the immediate ART group and 89% in the deferred ART group; P = .84), but there were significantly more grade 4 adverse events in the immediate ART arm (102 in the immediate ART group vs 87 in the deferred ART group; P = .04).
Immediate ART initiation does not improve outcome in patients presenting with HIV-associated tuberculous meningitis. There were significantly more grade 4 adverse events in the immediate ART arm, supporting delayed initiation of ART in HIV-associated tuberculous meningitis. Clinical Trials Registration. ISRCTN63659091.
目前尚不清楚开始抗逆转录病毒治疗（ART）的最佳时间是在人类免疫缺陷病毒（HIV）相关结核性脑膜炎患者中。
我们进行了一项随机、双盲、安慰剂对照试验，比较了 HIV 相关结核性脑膜炎患者中立即开始与延迟开始 ART 的效果，以确定立即开始 ART 是否可以降低死亡率。抗逆转录病毒药物（齐多夫定、拉米夫定和依非韦伦）在研究入组时或随机分组后 2 个月开始使用。所有患者均接受标准抗结核治疗、辅助地塞米松治疗以及预防性复方磺胺甲噁唑治疗，并随访 12 个月。我们进行了意向治疗、符合方案和预先指定的亚组分析。
共有 253 名患者被随机分配，其中 127 名患者分入立即 ART 组，126 名患者分入延迟 ART 组；在 9 个月内，立即 ART 组和延迟 ART 组分别有 76 名和 70 名患者死亡。立即开始 ART 与 9 个月时的死亡率（危险比[HR]，1.12；95%置信区间[CI]，0.81-1.55；P=0.50）或新发艾滋病事件或死亡时间（HR，1.16；95%CI，0.87-1.55；P=0.31）均无显著相关性。两组严重不良事件（3 级或 4 级）的发生率均较高（立即 ART 组为 90%，延迟 ART 组为 89%；P=0.84），但立即 ART 组的 4 级不良事件明显更多（立即 ART 组 102 例，延迟 ART 组 87 例；P=0.04）。
对于出现 HIV 相关结核性脑膜炎的患者，立即开始 ART 并不能改善其结局。立即 ART 组的 4 级不良事件明显更多，这支持在 HIV 相关结核性脑膜炎中延迟开始 ART。临床试验注册。ISRCTN63659091。
