Dual vs single protease inhibitor therapy following antiretroviral treatment failure - A randomized trial
Dual vs single protease inhibitor therapy following antiretroviral treatment failure - A randomized trial
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DOI：
10.1001/jama.288.2.169
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发表时间：
2002-07-10
影响因子：
120.7
通讯作者：
Mellors, JW
中科院分区：
文献类型：
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作者：
Hammer, SM;Vaida, F;Mellors, JW
背景管理抗逆转录病毒治疗失败的患者接受含蛋白酶抑制剂（PI）的方案是一个治疗的挑战。目的评估是否增加第二个PI提高抗病毒疗效的4种药物组合的病毒学失败的患者，而服用含PI的方案。设计多中心，随机，4臂试验，双盲和安慰剂对照的第二个PI，在1998年10月至2000年4月之间进行，其中有一个24周的初步分析扩展到48 wk.Setting三十一个参与艾滋病（获得性免疫缺陷综合征）临床试验单位在美国。参与者共481人免疫缺陷病毒（HIV）感染者与先前暴露于最多3 PI和病毒载量超过1000拷贝/mL。干预选择性随机分配（每先前PI暴露），以saquina。vir（n=116）;茚地那韦（n=69）;奈非那韦（n=139）;或安慰剂每天两次（n=157）;与安普那韦、阿巴卡韦、依法韦仑和阿德福韦酯联合，主要结果指标主要疗效分析涉及24周时病毒载量低于200拷贝/mL的比例。其他措施的变化，病毒载量和CD 4细胞计数从基线，不良事件，和HIV药物susceptibility.Results的481例患者中，148（31%）有一个病毒载量低于200拷贝/毫升在第24周。沙奎那韦、茚地那韦、奈非那韦和安慰剂组中病毒载量低于200拷贝/mL的患者比例分别为34%（40/116）、36%（25/69）、34%（47/139）和23%（36/157）。合并双PI组的比例高于安普那韦+安慰剂组（分别为35% [112/324] vs 23% [36/157]; P= 0.002）。总体而言，未接受过非核苷类逆转录酶抑制剂（NNRTI）治疗的患者中病毒载量低于200拷贝/mL的比例高于接受过NNRTI治疗的患者（分别为43% [116/270] vs 16% [33/ 211]; P
Context Management of antiretroviral treatment failure in patients receiving protease inhibitor (Pi)-containing regimens is a therapeutic challenge.Objective To assess whether adding a second PI improves antiviral efficacy of a 4-drug combination in patients with virologic failure while taking a PI-containing regimen.Design Multicenter, randomized, 4-arm trial, double-blind and placebo-controlled for second PI, conducted between October 1998 and April 2000, for which there was a 24-week primary analysis with extension to 48 weeks.Setting Thirty-one participating AIDS (acquired immunodeficiency syndrome) Clinical Trials Units in the United States. Participants A total of 481 human immunodeficiency virus (HIV)-infected persons with prior exposure to a maximum of 3 Pis and viral load above 1000 copies/mL.Intervention Selectively randomized assignment (per prior PI exposure) to saquina.. vir (n=116); indinavir (n=69); nelfinavir (n=139); or placebo twice per day (n=157); in combination with amprenavir, abacavir, efavirenz, and adefovir dipivoxii,.,Main Outcome Measures Primary efficacy analysis involved the proportion with viral load below 200 copies/mL at 24 weeks. Other measures were changes in viral load and CD4 cell count from baseline, adverse events, and HIV drug susceptibility.Results Of 481 patients, 148 (31%) had a Viral load below 200 copies/mL at week 24. The proportions of patients with a viral load below 200 copies/mL in, the saquinavir, indinavir, nelfinavir, and placebo arms were 34% (40/116), 36% (25/69), 34% (47/139), and 23% (36/157), respectively. The proportion in the combined dual-PI arms was higher than in the amprenavir-plus-placebo arm (35% [112/324] vs 23% [36/157], respectively; P=.002). Overall, a higher proportion of nonnucleoside reverse transcriptase inhibitor (NNRTI)-naive patients had a viral load below 200 copies/mL compared with NNRTI-experienced patients (43% [116/270] vs 16% [33/ 211], respectively; P