Durable efficacy of tipranavir-ritonavir in combination with an optimised background regimen of antiretroviral drugs for treatment-experienced HIV-1-infected patients at 48 weeks in the Randomized Evaluation of Strategic Intervention in multi-drug resistant patients with Tipranavir (RESIST) studies: an analysis of combined data from two randomised open-label trials
Durable efficacy of tipranavir-ritonavir in combination with an optimised background regimen of antiretroviral drugs for treatment-experienced HIV-1-infected patients at 48 weeks in the Randomized Evaluation of Strategic Intervention in multi-drug resistant patients with Tipranavir (RESIST) studies: an analysis of combined data from two randomised open-label trials
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DOI：
10.1016/s0140-6736(06)69154-x
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发表时间：
2006-08-05
期刊：
影响因子：
168.9
通讯作者：
Valdez, Hernan
中科院分区：
文献类型：
--
作者：
Hicks, Charles B.;Cahn, Pedro;Valdez, Hernan
背景：以前接受过广泛抗逆转录病毒治疗的HIV-1感染者的治疗选择有限。我们比较了新型非肽类蛋白酶抑制剂替普那韦与利托那韦联合使用外加优化背景方案与研究者选择的利托那韦增强比较蛋白酶抑制剂（cpi -利托那韦）在此类患者中的疗效和安全性。方法：我们对两项正在进行的、随机、开放标签、跨国、III期、RESIST研究的48周数据进行了综合分析。HIV-1感染成人具有3个月或更长时间的三次抗逆转录病毒治疗经验，两次或两次以上的蛋白酶抑制剂治疗方案，HIV-1 RNA每毫升1000拷贝或更高，并且基因典型地表现出对蛋白酶抑制剂的原发性耐药。主要终点是48周时治疗应答者的比例（在没有治疗改变的情况下，病毒载量比基线减少1 log / mL或更多）和48周至治疗失败的时间（意向治疗分析）。RESIST研究已在ClinicalTrials.gov注册，编号NCT00054717 （resistance -1）和NCT00144170 （resistance -2）。结果：共筛选3324例患者；746人接受替普那韦-利托那韦治疗，737人接受cpi -利托那韦治疗。486例（65.1%）使用替普那韦-利托那韦的患者和192例（26.1%）使用cpi -利托那韦的患者继续接受指定治疗，直到第48周。在第48周，与cpi -利托那韦组相比，更多的患者达到并维持了治疗反应(251例[33.6%]vs 113例[15.3%]
Background Treatment options for HIV-1 infected individuals who have received extensive previous antiretroviral therapy are limited. We compared efficacy and safety of the novel non-peptidic protease inhibitor tipranavir co-administered with ritonavir plus an optimised background regimen with that of an investigator-selected ritonavir-boosted comparator protease inhibitor (CPI-ritonavir) in such patients.Methods We did a combined analysis of 48-week data from two ongoing, randomised, open-label, multinational, phase III, RESIST studies. HIV-1-infected adults with 3 months or longer previous triple antiretroviral class experience, two or more previous protease inhibitor regimens, HIV-1 RNA 1000 copies per mL or greater, and genotypically demonstrated primary resistance to protease inhibitor, were eligible. Primary endpoints were proportion of treatment responders (with reduction in viral load of 1 log,, copies per mL or greater below baseline without treatment change) at 48 weeks and time to treatment failure through 48 weeks (intention-to-treat analysis). The RESIST studies are registered with ClinicalTrials.gov, numbers NCT00054717 (RESIST-1) and NCT00144170 (RESIST-2).Findings 3324 patients were screened; 746 received tipranavir-ritonavir and 737 CPI-ritonavir. 486 (65.1%) patients on tipranavir-ritonavir and 192 (26.1%) on CPI-ritonavir remained on assigned treatment until week 48. At week 48, more patients achieved and maintained treatment response in the tipranavir-ritonavir group than in the CPI-ritonavir group (251 [33.6%] vs 113 [15.3%]; p