奈韦拉平与阿扎那韦/利托那韦分别联合富马酸替诺福韦二吡呋酯/恩曲他滨用于初治HIV-1患者：ARTEN试验

Nevirapine versus atazanavir/ritonavir, each combined with tenofovir disoproxil fumarate/emtricitabine, in antiretroviral-naive HIV-1 patients: the ARTEN Trial.

作者信息

Soriano Vicente, Arastéh Keikawus, Migrone Horacio, Lutz Thomas, Opravil Milos, Andrade-Villanueva Jaime, Antunes Francisco, Di Perri Giovanni, Podzamczer Daniel, Taylor Steve, Domingo Pere, Gellermann Holger, de Rossi Lothar

机构信息

Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain.

出版信息

Antivir Ther. 2011;16(3):339-48. doi: 10.3851/IMP1745.

DOI:10.3851/IMP1745

PMID:21555816

Abstract

BACKGROUND

Selection of first-line antiretroviral therapy requires consideration of efficacy as well as effects on lipids given the increased concern about cardiovascular risk in HIV-1 patients.

METHODS

ARTEN is a randomized, open-label, non-inferiority trial that compares nevirapine (NVP) 200 mg twice daily or 400 mg once daily to atazanavir/ritonavir (ATZ/r) 300 mg/100 mg once daily, each combined with fixed-dose tenofovir disoproxil fumarate (TDF) 300 mg/emtricitabine (FTC) 200 mg once daily, in antiretroviral-naive HIV-1 patients with CD4(+) T-cell counts <400 (men) and <250 cells/mm(3) (women). The primary end point was plasma HIV RNA<50 copies/ml at two consecutive visits prior to week 48.

RESULTS

A total of 569 patients were randomized and treated. Overall, 66.8% of NVP and 65.3% of ATZ/r patients achieved the primary end point (difference 1.9%, 95% CI -5.9-9.8%). Similar rates of serious adverse events were observed (9.6% on NVP versus 8.8% on ATZ/r), although discontinuations due to adverse events were more frequent with NVP than ATZ/r (13.6% versus 3.6%, respectively). None of the 28 patients virologically failing ATZ/r selected resistance mutations, while they were selected in 29/44 patients virologically failing NVP. NVP induced a significantly greater increase in high-density lipoprotein cholesterol (HDL-c) and apolipoprotein A1 from baseline than ATZ/r, whereas triglycerides increased significantly more with ATZ/r than NVP. Mean change from baseline in TC:HDL-c ratio was -0.24 for NVP and 0.13 for ATZ/r (P=0.0001).

CONCLUSIONS

NVP demonstrated at week 48 non-inferior antiviral efficacy compared with ATZ/r when given along with TDF/FTC, despite more drug-related discontinuations with NVP than ATZ/r. NVP was associated with a lower atherogenic lipid profile than ATZ/r although resistance mutations were more frequently selected with NVP than ATZ/r.

摘要

背景

鉴于对HIV-1患者心血管风险的日益关注，一线抗逆转录病毒疗法的选择需要考虑疗效以及对血脂的影响。

方法

ARTEN是一项随机、开放标签、非劣效性试验，比较了每日两次200毫克或每日一次400毫克的奈韦拉平（NVP）与每日一次300毫克/100毫克的阿扎那韦/利托那韦（ATZ/r），每种药物均与固定剂量的富马酸替诺福韦二吡呋酯（TDF）300毫克/恩曲他滨（FTC）200毫克每日一次联合使用，用于CD4(+)T细胞计数<400（男性）和<250个细胞/立方毫米（女性）的初治HIV-1患者。主要终点是在第48周之前连续两次访视时血浆HIV RNA<50拷贝/毫升。

结果

共有569名患者被随机分组并接受治疗。总体而言，66.8%的NVP患者和65.3%的ATZ/r患者达到了主要终点（差异1.9%，95%CI -5.9-9.8%）。观察到严重不良事件的发生率相似（NVP组为9.6%，ATZ/r组为8.8%），尽管因不良事件停药的情况在NVP组比ATZ/r组更频繁（分别为13.6%和3.6%）。在28例ATZ/r病毒学失败的患者中，没有一例选择耐药突变，而在44例NVP病毒学失败的患者中有29例选择了耐药突变。与ATZ/r相比，NVP从基线开始使高密度脂蛋白胆固醇（HDL-c）和载脂蛋白A1显著增加，而ATZ/r使甘油三酯的增加显著高于NVP。NVP组TC:HDL-c比值从基线的平均变化为-0.24，ATZ/r组为0.13（P=0.0001）。