Faculty of Medicine, University of British Columbia, 1081 Burrard St., Vancouver, BC, Canada.
Expert Opin Pharmacother. 2010 Jun;11(8):1433-7. doi: 10.1517/14656561003724754.
Therapeutic options for treatment-experienced HIV-infected patients have been limited. The DUET trial evaluated the use of etravirine, a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI), or placebo, in 1203 treatment-experienced, HIV-infected patients. Eligible patients had to have evidence of NNRTI and protease inhibitor resistance-associated mutations, and evidence of virologic failure, as defined as a plasma viral load > 5000 copies/ml on antiretroviral therapy at the time of screening. Patients in both arms received an optimized background regimen including darunavir/ritonavir. DUET demonstrated superior outcomes in virologic suppression (plasma viral load < 50 copies/ml) and clinical end points including new AIDS-defining illnesses and death, in those randomized to receive etravirine. These results were maintained at 48 weeks of follow-up. Furthermore, etravirine was shown to be safe and well-tolerated over this period. In exploratory analyses, patients in the DUET study with greater number of active agents within the background regimen were more likely to have a fully suppressive response. Taken together, the DUET results highlight the high rates of virological success that can be achieved using new active agents, such as ritonavir-boosted darunavir and etravirine, in treatment-experienced patients with underlying drug-resistant HIV infection.
治疗经验丰富的 HIV 感染者的治疗选择有限。DUET 试验评估了依曲韦林（一种第二代非核苷类逆转录酶抑制剂（NNRTI））或安慰剂在 1203 例治疗经验丰富的 HIV 感染患者中的应用。合格的患者必须有 NNRTI 和蛋白酶抑制剂耐药相关突变的证据，以及病毒学失败的证据，定义为在筛选时接受抗逆转录病毒治疗时血浆病毒载量>5000 拷贝/ml。接受依曲韦林治疗的患者在接受达拉韦林/利托那韦优化背景方案的基础上进行治疗。DUET 研究表明，在病毒学抑制（血浆病毒载量<50 拷贝/ml）和临床终点方面，包括新发艾滋病定义性疾病和死亡，接受依曲韦林治疗的患者具有更好的结果。这些结果在 48 周的随访中得到了维持。此外，在这段时间内，依曲韦林被证明是安全且耐受良好的。在探索性分析中，背景方案中活性药物数量较多的 DUET 研究患者更有可能出现完全抑制反应。综上所述，DUET 研究结果突出了使用新的活性药物（如利托那韦增强的达芦那韦和依曲韦林）在具有潜在耐药性 HIV 感染的治疗经验丰富的患者中可以实现高病毒学成功率。
