Comparison of sequential three-drug regimens as initial therapy for HIV-1 infection
Comparison of sequential three-drug regimens as initial therapy for HIV-1 infection
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DOI：
10.1056/nejmoa030264
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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：
Robbins, GK;De Gruttola, V;Doolan, A
背景：治疗人类免疫缺陷病毒1型（HIV-1）感染的抗逆转录病毒治疗方案的最佳顺序尚不清楚。我们比较了几种不同的抗逆转录病毒治疗strategy.METHODS：这个多中心，随机，部分双盲试验采用析因设计，比较对序贯三种药物的方案，开始与一个方案，包括齐多夫定和拉米夫定或方案，包括去羟肌苷和司他夫定结合奈非那韦或依法韦仑。主要终点是失败的第二个三种药物regiments.Results的时间长度：共620例以前没有接受过抗逆转录病毒治疗的受试者进行了随访，中位数为2.3年。开始时采用三种药物方案，包括依法韦仑联合齐多夫定和拉米夫定与以奈非那韦为起始药物的方案相比，（第二种方案失败的风险比为0.71; 95%置信区间，0.48至1.06），以及延迟第二次病毒学失败（风险比，0.56; 95%置信区间，0.29至1.09），并显着延迟失败的第一个方案（风险比，0.39）和第一个病毒学失败（风险比，0.34）。从齐多夫定和拉米夫定联合依法韦仑开始与去羟肌苷和司他夫定相比，（风险比，0.68），并显着延迟了第一次和第二次病毒学失败（第一次病毒学失败的风险比，0.39;第二次病毒学失败的风险比，0.47），以及第一次治疗方案的失败（风险比，0.35）。最初使用齐多夫定、拉米夫定和依法韦仑可以缩短病毒抑制时间。结论：抗逆转录病毒药物的疗效取决于它们的组合方式。在本研究中，齐多夫定、拉米夫定和依法韦仑联合治疗上级其他抗逆转录病毒治疗方案。
BACKGROUND:The optimal sequencing of antiretroviral regimens for the treatment of infection with human immunodeficiency virus type 1 (HIV-1) is unknown. We compared several different antiretroviral treatment strategies.METHODS:This multicenter, randomized, partially double-blind trial used a factorial design to compare pairs of sequential three-drug regimens, starting with a regimen including zidovudine and lamivudine or a regimen including didanosine and stavudine in combination with either nelfinavir or efavirenz. The primary end point was the length of time to the failure of the second three-drug regimen.RESULTS:A total of 620 subjects who had not previously received antiretroviral therapy were followed for a median of 2.3 years. Starting with a three-drug regimen containing efavirenz combined with zidovudine and lamivudine (but not efavirenz combined with didanosine and stavudine) appeared to delay the failure of the second regimen, as compared with starting with a regimen containing nelfinavir (hazard ratio for failure of the second regimen, 0.71; 95 percent confidence interval, 0.48 to 1.06), as well as to delay the second virologic failure (hazard ratio, 0.56; 95 percent confidence interval, 0.29 to 1.09), and significantly delayed the failure of the first regimen (hazard ratio, 0.39) and the first virologic failure (hazard ratio, 0.34). Starting with zidovudine and lamivudine combined with efavirenz (but not zidovudine and lamivudine combined with nelfinavir) appeared to delay the failure of the second regimen, as compared with starting with didanosine and stavudine (hazard ratio, 0.68), and significantly delayed both the first and the second virologic failures (hazard ratio for the first virologic failure, 0.39; hazard ratio for the second virologic failure, 0.47), as well as the failure of the first regimen (hazard ratio, 0.35). The initial use of zidovudine, lamivudine, and efavirenz resulted in a shorter time to viral suppression.CONCLUSIONS:The efficacy of antiretroviral drugs depends on how they are combined. The combination of zidovudine, lamivudine, and efavirenz is superior to the other antiretroviral regimens used as initial therapy in this study.