Once-daily atazanavir/ritonavir versus twice-daily lopinavir/ritonavir, each in combination with tenofovir and erntricitabine, for management of antiretroviral-naive HIV-1-infected patients: 48 week efficacy and safety results of the CASTLE study-猫眼课题宝

DOI：

10.1016/s0140-6736(08)61081-8

发表时间：

2008-08-23

期刊：

LANCET

影响因子：

168.9

通讯作者：

中科院分区：

医学1区

文献类型：

作者：

Molina, Jean-Michel;Andrade-Villanueva, Jaime;McGrath, Donnie

背景阿扎那韦/利托那韦与洛匹那韦/利托那韦一样有效，在治疗经历的hiv -1感染患者中具有更有利的脂质特征和更小的胃肠道毒性。我们在未接受治疗的患者中直接比较了这两种组合。方法在这项开放标签的国际非效性研究中，883例hiv -1感染的抗逆转录病毒初始患者被随机分配接受阿扎那韦/利托那韦300/ 100mg每日1次（n=440）或洛匹那韦/利托那韦400/ 100mg每日2次（n=443），联合固定剂量替诺福韦/恩曲他滨300/ 200mg每日1次。随机化采用计算机生成的集中随机化计划进行，并按HIV RNA（病毒载量）基线水平和地理区域分层。主要终点是48周时病毒载量低于50拷贝/ mL的患者比例。主要疗效分析以意向治疗为主。该试验已在ClinicalTrials.gov注册，注册号为NCT00272779。在第48周，440名接受阿扎那韦/利托那韦治疗的患者中有343名（78%）和443名接受洛匹那韦/利托那韦治疗的患者中有338名（76%）的病毒载量低于50拷贝/ mL（差异1.7%,95% CI -3.8至7.1）。与基线相比，CD4细胞计数的平均增加相似（阿扎那韦/利托那韦组每pL 203个细胞，洛匹那韦/利托那韦组每pL 219个细胞）。阿扎那韦/利托那韦组25例（6%）患者和洛匹那韦/利托那韦组26例（6%）患者在48周时出现病毒学失败。在阿扎那韦/利托那韦组中，只有两名患者在治疗后出现非多态性蛋白酶抑制剂耐药突变，这使一名患者对阿扎那韦产生了表型耐药。阿扎那韦/利托那韦组441例患者中有51例（12%）出现严重不良事件，洛匹那韦/利托那韦组437例患者中有42例（10%）出现严重不良事件。阿扎那韦/利托那韦组出现2-4级治疗相关腹泻（10例[2%]vs 50例[11%]）和恶心（17例[4%]vs 33例[8%]）的患者少于洛匹那韦/利托那韦组。阿扎那韦/利托那韦组441例患者中有16例（458例）出现2-4级黄疸，而洛匹那韦/利托那韦组437例患者中没有出现黄疸；435例阿扎那韦/利托那韦患者中有146例（34%）出现总胆红素3-4级升高，1例(

Background Atazanavir/ritonavir is as effective as lopinavir/ritonavir, with a more favourable lipid profile and less gastrointestinal toxicity, in treatment-experienced HIV-1-infected patients. We compared these two combinations directly in treatment-naive patients.Methods In this open-label, international non-inferiority study, 883 antiretroviral-naive, HIV-1-infected patients were randomly assigned to receive atazanavir/ritonavir 300/100 mg once daily (n=440) or lopinavir/ritonavir 400/100 mg twice daily (n=443), in combination with fixed-dose tenofovir/emtricitabine 300/200 mg once daily. Randomisation was done with a computer-generated centralised randomisation schedule and was stratified by baseline levels of HIV RNA (viral load) and geographic region. The primary endpoint was the proportion of patients with viral load less than 50 copies per mL at week 48. The main efficacy analysis was done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00272779.Findings At week 48, 343 (78%) of 440 patients receiving atazanavir/ritonavir and 338 (76%) of 443 patients receiving lopinavir/ritonavir had achieved a viral load of less than 50 copies per mL (difference 1.7%, 95% CI -3.8 to 7.1). Mean increases from baseline in CD4 cell count were similar (203 cells per pL in the atazanavir/ritonavir group vs 219 cells per pL in the lopinavir/ritonavir group). 25 (6%) patients in the atazanavir/ritonavir group and 26 (6%) in the lopinavir/ ritonavir group were virological failures by week 48. Only two patients, both in the atazanavir/ritonavir group, had non-polymorphic protease inhibitor resistance mutations emerge oil treatment, which conferred phenotypic resistance to atazanavir in one patient. Serious adverse events were noted in 51 (12%) of 441 patients in the atazanavir/ritonavir group and in 42 (10%) of 437 patients in the lopinavir/ritonavir group. Fewer patients in the atazanavir/ritonavir group than in the lopinavir/ritonavir group experienced grade 2-4 treatment-related diarrhoea (10 [2%] vs 50 [11%]) and nausea (17 [4%] vs 33 [8%]). Grade 2-4 jaundice was seen in 16 (458) of 441 patients in the atazanavir/ritonavir group versus none of 437 patients in the lopinavir/ritonavir group; grade 3-4 increases in total bilirubin were seen in 146 (34%) of 435 patients on atazanavir/ritonavir and in one (

Once-daily atazanavir/ritonavir versus twice-daily lopinavir/ritonavir, each in combination with tenofovir and erntricitabine, for management of antiretroviral-naive HIV-1-infected patients: 48 week efficacy and safety results of the CASTLE study

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