Lazzarin Adriano, Campbell Thomas, Clotet Bonaventura, Johnson Margaret, Katlama Christine, Moll Arend, Towner William, Trottier Benoit, Peeters Monika, Vingerhoets Johan, de Smedt Goedele, Baeten Benny, Beets Greet, Sinha Rekha, Woodfall Brian
Vita-Salute, San Raffaele University, Milan, Italy.
Lancet. 2007 Jul 7;370(9581):39-48. doi: 10.1016/S0140-6736(07)61048-4.
TMC125 (etravirine) is a non-nucleoside reverse-transcriptase inhibitor (NNRTI) with activity against NNRTI-resistant HIV-1 in phase IIb trials. The aim of DUET-2 is to examine the efficacy, tolerability, and safety of TMC125 in treatment-experienced patients.
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 mutations 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 endpoint 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.
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.
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.
TMC125（依曲韦林）是一种非核苷类逆转录酶抑制剂（NNRTI），在IIb期试验中对耐NNRTI的HIV-1具有活性。DUET-2试验的目的是研究TMC125在经治患者中的疗效、耐受性和安全性。
在这项持续进行的随机、双盲、安慰剂对照的III期试验中，接受抗逆转录病毒治疗效果不佳且对现有NNRTIs耐药并有至少三种主要蛋白酶抑制剂突变证据的HIV-1感染患者，若接受稳定（8周未改变）的抗逆转录病毒治疗且血浆HIV-1 RNA大于每毫升5000拷贝，则有资格入选。患者被随机分配接受TMC125（200毫克）或安慰剂治疗，均每日两次，同时服用达芦那韦-利托那韦、研究者选择的核苷/核苷酸逆转录酶抑制剂以及可选的恩夫韦肽。主要终点是在第24周时病毒载量确认低于每毫升50拷贝的患者比例（采用美国食品药品监督管理局的病毒学应答丧失时间算法）。分析采用意向性治疗。本试验已在ClinicalTrials.gov注册，编号为NCT00255099。
591例患者被随机分组并接受治疗（TMC125组295例，安慰剂组296例）。到第24周时，TMC125组有51例（17%）患者和安慰剂组有73例（25%）患者停药，主要原因是病毒学失败。在第24周时，TMC125组有183例（62%）患者和安慰剂组有129例（44%）患者病毒载量确认低于每毫升50拷贝（差异为18%，95%可信区间为11 - 26；p = 0.0003）。两组不良事件的类型和发生率大致相同。
在经治患者中，TMC125治疗在第24周时比安慰剂导致更好的病毒学抑制效果。TMC125的安全性和耐受性总体上与安慰剂相当。
