Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial
Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial
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DOI：
10.1016/s0140-6736(09)60918-1
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发表时间：
2009-09-05
期刊：
影响因子：
168.9
通讯作者：
Sklar, Peter
中科院分区：
文献类型：
--
作者：
Lennox, Jeffrey L.;Dejesus, Edwin;Sklar, Peter
背景
在有多种药物耐药的HIV - 1感染且有治疗经验的患者中，雷特格韦与最佳的基础治疗联合使用是有效的且耐受性良好。我们比较了雷特格韦与依非韦伦作为联合抗逆转录病毒疗法的一部分在初治患者中的安全性和疗效。
方法
来自五大洲67个研究中心的患者在2006年9月14日至2008年6月5日期间入组。符合条件的患者感染了HIV - 1，病毒RNA（vRNA）浓度超过每毫升5000拷贝，且对依非韦伦、替诺福韦或恩曲他滨无基线耐药。患者通过交互式语音应答系统按1∶1的比例（双盲）随机分配，接受每日两次口服400毫克雷特格韦或每日一次口服600毫克依非韦伦，并联合使用替诺福韦和恩曲他滨。主要疗效终点是在第48周时vRNA浓度达到低于每毫升50拷贝。主要分析是按照方案分析。非劣效性界限为12%。本研究在ClinicalTrials.gov注册，编号为NCT00369941。
结果
566名患者入组并随机分配接受治疗，其中281名接受雷特格韦治疗，282名接受依非韦伦治疗，3名从未接受治疗。在基线时，297名（53%）患者的vRNA拷贝数超过每毫升100000拷贝，267名（47%）患者的CD4细胞计数为每微升200个细胞或更少。主要分析（未完成治疗计为失败）显示，雷特格韦组86.1%（n = 241名患者）和依非韦伦组81.9%（n = 230）达到主要终点（差异4.2%，95%置信区间 - 1.9至10.3）。雷特格韦组患者达到病毒抑制的时间比依非韦伦组更短（对数秩检验p……（此处原文似乎不完整）
Background Use of raltegravir with optimum background therapy is effective and well tolerated in treatment-experienced patients with multidrug-resistant HIV-1 infection. We compared the safety and efficacy of raltegravir with efavirenz as part of combination antiretroviral therapy for treatment-naive patients.Methods Patients from 67 study centres on five continents were enrolled between Sept 14, 2006, and June 5, 2008. Eligible patients were infected with HIV-1, had viral RNA (vRNA) concentration of more than 5000 copies per mL, and no baseline resistance to efavirenz, tenofovir, or emtricitabine. Patients were randomly allocated by interactive voice response system in a 1:1 ratio (double-blind) to receive 400 mg oral raltegravir twice daily or 600 mg oral efavirenz once daily, in combination with tenofovir and emtricitabine. The primary efficacy endpoint was achievement of a vRNA concentration of less than 50 copies per mL at week 48. The primary analysis was per protocol. The margin of non-inferiority was 12%. This study is registered with ClinicalTrials.gov, number NCT00369941.Findings 566 patients were enrolled and randomly allocated to treatment, of whom 281 received raltegravir, 282 received efavirenz, and three were never treated. At baseline, 297 (53%) patients had more than 100 000 vRNA copies per mL and 267 (47%) had CD4 counts of 200 cells per mu L or less. The main analysis (with non-completion counted as failure) showed that 86.1% (n=241 patients) of the raltegravir group and 81.9% (n=230) of the efavirenz group achieved the primary endpoint (difference 4.2%, 95% CI -1.9 to 10.3). The time to achieve such viral suppression was shorter for patients on raltegravir than on efavirenz (log-rank test p