Gathe Joseph, Cooper David A, Farthing Charles, Jayaweera Dushyantha, Norris Dorece, Pierone Gerald, Steinhart Corklin R, Trottier Benoit, Walmsley Sharon L, Workman Cassy, Mukwaya Geoffrey, Kohlbrenner Veronika, Dohnanyi Catherine, McCallister Scott, Mayers Douglas
Therapeutic Concepts, Houston, TX 77004, USA.
Clin Infect Dis. 2006 Nov 15;43(10):1337-46. doi: 10.1086/508353. Epub 2006 Oct 17.
Improved treatment options are needed for patients infected with multidrug-resistant human immunodeficiency virus type 1 (HIV-1). The nonpeptidic protease inhibitor tipranavir has demonstrated antiviral activity against many protease inhibitor-resistant HIV-1 isolates. The Randomized Evaluation of Strategic Intervention in multi-drug reSistant patients with Tipranavir (RESIST-1) trial is an ongoing, open-label study comparing the efficacy and safety of ritonavir-boosted tipranavir (TPV/r) with an investigator-selected ritonavir-boosted comparator protease inhibitor (CPI/r) in treatment-experienced, HIV-1-infected patients.
Six hundred twenty antiretroviral-experienced patients were treated at 125 sites in North America and Australia. Before randomization, all patients underwent genotypic resistance testing, which investigators used to select a CPI/r and an optimized background regimen. Patients were randomized to receive TPV/r or CPI/r and were stratified on the basis of preselected protease inhibitor and enfuvirtide use. Treatment response was defined as a confirmed reduction in the HIV-1 load of > or = 1 log10 less than the baseline level without treatment change at week 24.
Mean baseline HIV-1 loads and CD4+ cell counts were 4.74 log10 copies/mL and 164 cells/mm3, respectively. At week 24, a total of 41.5% of patients in the TPV/r arm and 22.3% in the CPI/r arm had a > or = 1-log10 reduction in the HIV-1 load (intent-to-treat population; P<.0001). Mean increases in the CD4+ cell count of 54 and 24 cells/mm3 occurred in the TPV/r and CPI/r groups, respectively. Adverse events were slightly more common in the TPV/r group and included diarrhea, nausea, and vomiting. Elevations in alanine and aspartate aminotransferase levels and in cholesterol/triglyceride levels were more frequent in the TPV/r group.
TPV/r demonstrated superior antiviral activity, compared with investigator-selected, ritonavir-boosted protease inhibitors, at week 24 in treatment-experienced patients with multidrug-resistant HIV-1 infection.
对于感染多重耐药1型人类免疫缺陷病毒（HIV-1）的患者，需要有更好的治疗选择。非肽类蛋白酶抑制剂替拉那韦已显示出对许多耐蛋白酶抑制剂的HIV-1分离株具有抗病毒活性。替拉那韦在多重耐药患者中的随机策略干预评估（RESIST-1）试验是一项正在进行的开放标签研究，比较了利托那韦增强的替拉那韦（TPV/r）与研究者选择的利托那韦增强的对照蛋白酶抑制剂（CPI/r）在有治疗经验的HIV-1感染患者中的疗效和安全性。
620名有抗逆转录病毒治疗经验的患者在北美和澳大利亚的125个地点接受治疗。在随机分组前，所有患者均接受基因型耐药检测，研究者据此选择一种CPI/r和一种优化的背景治疗方案。患者被随机分配接受TPV/r或CPI/r，并根据预先选定的蛋白酶抑制剂和恩夫韦肽的使用情况进行分层。治疗反应定义为在第24周时HIV-1载量确认降低≥1 log10且低于基线水平，同时未改变治疗方案。
基线时HIV-1载量的平均值和CD4+细胞计数分别为4.74 log10拷贝/mL和164个细胞/mm3。在第24周时，TPV/r组共有41.5%的患者HIV-1载量降低≥1 log10，CPI/r组为22.3%（意向性治疗人群；P<0.0001）。TPV/r组和CPI/r组的CD4+细胞计数平均分别增加了54个和24个细胞/mm3。不良事件在TPV/r组中略为常见，包括腹泻、恶心和呕吐。TPV/r组中丙氨酸和天冬氨酸转氨酶水平以及胆固醇/甘油三酯水平升高更为频繁。
在有治疗经验的多重耐药HIV-1感染患者中，在第24周时，与研究者选择的利托那韦增强的蛋白酶抑制剂相比，TPV/r显示出更强的抗病毒活性。
