Triple-nucleoside regimens versus efavirenz-containing regimens for the initial treatment of HIV-1 infection
Triple-nucleoside regimens versus efavirenz-containing regimens for the initial treatment of HIV-1 infection
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DOI：
10.1056/nejmoa031772
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发表时间：
2004-04-29
影响因子：
158.5
通讯作者：
Kuritzkes, DR
中科院分区：
文献类型：
--
作者：
Gulick, RM;Ribaudo, HJ;Kuritzkes, DR
方案包含三个核苷逆转录酶抑制剂提供了一种替代方案，含有非核苷逆转录酶抑制剂或蛋白酶抑制剂的人类免疫缺陷病毒1型（HIV-1）感染的初始治疗方案，但直接比较的数据是有限的。齐多夫定-拉米夫定-阿巴卡韦、齐多夫定-拉米夫定+依法韦仑和齐多夫定-拉米夫定-阿巴卡韦+依法韦仑。我们总共招募了1147名受试者，平均基线HIV-1 RNA水平为4.85 log（10）（71，434）拷贝/毫升，平均CD 4细胞计数为238/立方毫米。数据和安全性监测委员会使用预先规定的停止界限进行了计划审查，建议停止三核苷组，并将三核苷组的结果与依法韦仑组的汇总数据进行比较。中位随访32周后，三核苷组382名受试者中有82名（21%）和联合依法韦仑组765名受试者中有85名（11%）出现病毒学失败;三核苷组病毒学失败的时间明显较短（P < 0.001）。无论治疗前HIV-1 RNA分层如何（至少100，000拷贝/mL或低于该水平;两次比较的P ≤ 0.001），均观察到该差异。CD 4细胞计数和3级或4级不良事件的发生率的变化并没有显着差异groups.CONCLUSIONSIn HIV-1感染的初始治疗，阿巴卡韦，齐多夫定，拉米夫定的三核苷组合的试验是病毒学劣于一个方案，含有依法韦仑和两个或三个核苷。
BACKGROUNDRegimes containing three nucleoside reverse-transcriptase inhibitors offer an alternative to regimes containing nonnucleoside reverse-transcriptase inhibitors or protease inhibitors for the initial treatment of human immunodeficiency virus type 1 (HIV-1) infection, but data from direct comparisons are limited.METHODSThis randomized, double-blind study involved three antiretroviral regimens for the initial treatment of subjects infected with HIV-1: zidovudine - lamivudine - abacavir, zidovudine - lamivudine plus efavirenz, and zidovudine - lamivudine - abacavir plus efavirenz.RESULTSWe enrolled a total of 1147 subjects with a mean baseline HIV-1 RNA level of 4.85 log(10) (71,434) copies per milliliter and a mean CD4 cell count of 238 per cubic millimeter were enrolled. A scheduled review by the data and safety monitoring board with the use of prespecified stopping boundaries led to a recommendation to stop the triple-nucleoside group and to present the results in the triple-nucleoside group in comparison with pooled data from the efavirenz groups. After a median follow-up of 32 weeks, 82 of 382 subjects in the triple-nucleoside group (21 percent) and 85 of 765 of those in the combined efavirenz groups (11 percent) had virologic failure; the time to virologic failure was significantly shorter in the triple-nucleoside group (P < 0.001). This difference was observed regardless of the pretreatment HIV-1 RNA stratum (at least 100,000 copies per milliliter or below this level; P ≤ 0.001 for both comparisons). Changes in the CD4 cell count and the incidence of grade 3 or grade 4 adverse events did not differ significantly between the groups.CONCLUSIONSIn this trial of the initial treatment of HIV-1 infection, the triple-nucleoside combination of abacavir, zidovudine, and lamivudine was virologically inferior to a regimen containing efavirenz and two or three nucleosides.