Comparison of four-drug regimens and pairs of sequential three-drug regimens as initial therapy for HIV-1 infection
Comparison of four-drug regimens and pairs of sequential three-drug regimens as initial therapy for HIV-1 infection
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DOI：
10.1056/nejmoa030265
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发表时间：
2003-12-11
影响因子：
158.5
通讯作者：
Doolan, A
中科院分区：
文献类型：
--
作者：
Shafer, RW;Smeaton, LM;Doolan, A
背景：目前尚不清楚人类免疫缺陷病毒1型(HIV-1)的治疗应该从四种药物开始，还是两种连续的三种药物方案。方法：在这项多中心试验中，我们比较了最初的四种药物方案，其中包含依法韦伦和奈非那韦，联合使用地丹诺辛和司他夫定，或齐多夫定和拉米夫定，以及使用两种连续的三种药物方案，第一种三种药物方案包含依法韦伦或奈非那韦。结果：总共980名受试者被跟踪治疗，中位数为2.3年。在接受含有地达诺辛、司他夫定、奈非那韦和伊法韦仑的四种药物方案的组和接受从地丹诺辛、司他夫定和奈非那韦开始的三种药物方案(方案失败的风险比为1.24)或地达诺辛、司他夫定和法韦伦的组之间，方案失败的发生率没有显著差异(危险比为1.01)。接受包含齐多夫定、拉米夫定、奈非那韦和依法韦仑的四药方案的组与接受从齐多夫定、拉米夫定和奈非那韦开始的三种药物方案的组(危险比为1.06)或齐多夫定、拉米夫定和法韦伦的组(危险比为1.45)之间没有显著差异。四联用药方案导致第一次方案失败的时间比三联用药方案更长(第一联用失败的风险比为0.55)；四联用药方案包括地达诺辛、司他夫定和伊法韦林(风险比为0.63)；或齐多夫定、拉米夫定和奈非那韦(危险比为0.49)，但含有齐多夫定、拉米夫定和依法韦林的三联用药方案(危险比为1.21)与三联用药方案相比，HIV-1成功治疗的持续时间没有显著差异。在这些治疗策略中，以齐多夫定、拉米夫定和依法韦仑三联用药方案启动治疗是最佳选择。
BACKGROUND:It is unclear whether therapy for human immunodeficiency virus type 1 (HIV-1) should be initiated with a four-drug or two sequential three-drug regimens.METHODS:In this multicenter trial we compared initial therapy involving four-drug regimens containing efavirenz and nelfinavir in combination with either didanosine and stavudine or zidovudine and lamivudine with therapy involving two consecutive three-drug regimens the first of which contained either efavirenz or nelfinavir.RESULTS:A total of 980 subjects were followed for a median of 2.3 years. There was no significant difference in the occurrence of regimen failures between the group that received the four-drug regimen containing didanosine, stavudine, nelfinavir, and efavirenz and the groups that received the three-drug regimens beginning with didanosine, stavudine, and nelfinavir (hazard ratio for regimen failure, 1.24) or didanosine, stavudine, and efavirenz (hazard ratio, 1.01). There was no significant difference between the group that received the four-drug regimen containing zidovudine, lamivudine, nelfinavir, and efavirenz and the groups that received the three-drug regimens beginning with zidovudine, lamivudine, and nelfinavir (hazard ratio, 1.06) or zidovudine, lamivudine, and efavirenz (hazard ratio, 1.45). A four-drug regimen was associated with a longer time to the first regimen failure than the three-drug regimens containing didanosine, stavudine, and nelfinavir (hazard ratio for a first regimen failure, 0.55); didanosine, stavudine, and efavirenz (hazard ratio, 0.63); or zidovudine, lamivudine, and nelfinavir (hazard ratio, 0.49), but not the three-drug regimen containing zidovudine, lamivudine, and efavirenz (hazard ratio, 1.21).CONCLUSIONS:There was no significant difference in the duration of successful HIV-1 treatment between a single four-drug regimen and two consecutive three-drug regimens. Among these treatment strategies, initiating therapy with the three-drug regimen of zidovudine, lamivudine, and efavirenz is the optimal choice.