Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-2: 24-week results from a randomised, double-blind, placebo-controlled trial
Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-2: 24-week results from a randomised, double-blind, placebo-controlled trial
复制标题
DOI：
10.1016/s0140-6736(07)61048-4
复制
发表时间：
2007-07-07
期刊：
影响因子：
168.9
通讯作者：
Woodfall, Brian
中科院分区：
文献类型：
--
作者：
Lazzarin, Adriano;Campbell, Thomas;Woodfall, Brian
背景TMC 125（依曲韦林）是一种非核苷类逆转录酶抑制剂（NNRTI），在IIb期试验中对NNRTI耐药的HfV-1具有活性。DUET-2的目的是研究TMC 125在治疗经验丰富的patients.Methods中的疗效、耐受性和安全性。在这项持续的随机、双盲、安慰剂对照、III期试验中，HIV-1感染患者在抗逆转录病毒治疗失败后，对目前可用的NNRTI和至少三种主要蛋白酶抑制剂穆塔有耐药性的证据：如果接受稳定（8周不变）抗逆转录病毒治疗且血浆HIV-1 RNA大于5000拷贝/mL，则符合入组条件。患者被随机分配接受TMC 125（200 mg）或安慰剂，每天两次，分别与地芦那韦-利托那韦、选择性核苷/核苷酸逆转录酶抑制剂和可选的恩夫韦肽联合给药。主要终点是第24周时确认病毒载量低于50拷贝/mL的患者比例（FDA至病毒学应答丧失时间算法）。该试验在ClinicalTrials.gov注册，编号NCT 00255099。结果591例患者接受随机化和治疗（295例患者在TMC 125组，296例在安慰剂组）。到第24周，TMC 125组中的51名（17%）患者和安慰剂组中的73名（25%）患者停止了治疗，主要是因为病毒学失败。第24周，TMC 125组183例（62%）患者和安慰剂组129例（44%）患者确认病毒载量低于50拷贝/mL（差异18%，95% CI 11-26; p = 0.0003）。不良事件的类型和频率在两组中大致相同。解释在有治疗经验的患者中，与安慰剂相比，用TMC 125治疗在第24周导致更好的病毒学抑制。TMC 125的安全性和耐受性特征通常与安慰剂相当。
Background TMC125 (etravirine) is a non-nucleoside reverse-transcriptase inhibitor (NNRTI) with activity against NNRTI-resistant HfV-1 in phase IIb trials. The aim of DUET-2 is to examine the efficacy, tolerability, and safety of TMC125 in treatment-experienced patients.Methods In this continuing randomised, double-blind, placebo-controlled, phase III trial, HIV-1-infected patients on failing antiretroviral therapy with evidence of resistance to currently available NNRTIs and at least three primary protease inhibitor muta:ions were eligible for enrolment if on stable (8 weeks unchanged) antiretroviral therapy with plasma HIV-1 RNA greater than 5000 copies per mL. Patients were randomly assigned to receive either TMC125 (200 mg) or placebo, each given twice daily with darunavir-ritonavir, investigator-selected nucleoside/nucleotide reverse transcriptase inhibitors, and optional enfuvirtide. The primary endpornt was the proportion of patients with confirmed viral load below 50 copies per mL at week 24 (FDA time-to-loss of virological response algorithm). Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00255099.Findings 591 patients were randomised and treated (295 patients in the TMC125 group and 296 in the placebo group). By week 24, 51 (17%) patients in the TMC125 group and 73 (25%) in the placebo group had discontinued, mainly because of virological failure. 183 (62%) patients in the TMC125 group and 129 (44%) in the placebo group achieved confirmed viral load below 50 copies per mL at week 24 (difference 18%, 95% CI 11-26; p = 0.0003). The type and frequency of adverse events were: much the same in the two groups.Interpretation In treatment-experienced patients, treatment with TMC125 led to better virological suppression at week 24 than did placebo. The safety and tolerability profile of TMC125 was generally comparable with placebo.