Dolutegravir plus Abacavir-Lamivudine for the Treatment of HIV-1 Infection
Dolutegravir plus Abacavir-Lamivudine for the Treatment of HIV-1 Infection
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DOI：
10.1056/nejmoa1215541
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发表时间：
2013-11-07
影响因子：
158.5
通讯作者：
Nichols, Garrett
中科院分区：
文献类型：
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作者：
Walmsley, Sharon L.;Antela, Antonio;Nichols, Garrett
dolutegravir （S/GSK1349572）是一种每日一次的非强化整合酶抑制剂，最近在美国被批准用于与其他抗逆转录病毒药物联合治疗人类免疫缺陷病毒1型（HIV-1）感染。Dolutegravir与abacvir -lamivudine联合可能提供一种简化的治疗方案。方法：我们进行了一项随机、双盲、3期研究，涉及未接受过HIV-1感染治疗且HIV-1 RNA水平为每毫升1000拷贝或更高的成人参与者。参与者被随机分配到50mg剂量的多替格拉韦加阿巴卡韦-拉米夫定每日一次（DTG-ABC-3TC组）或与依非韦伦-替诺福韦-富马酸二氧吡酯(DF)-恩曲他滨每日一次（EFV-TDF-FTC组）联合治疗。主要终点是48周时HIV-1 RNA水平低于50拷贝/毫升的参与者比例。次要终点包括病毒抑制的时间，CD4+ t细胞计数从基线的变化，安全性和病毒耐药性。结果共有833名参与者接受了至少一剂研究药物。在第48周，DTG-ABC-3TC组中HIV-1 RNA水平低于50拷贝/毫升的参与者比例显著高于EFV-TDF-FTC组（88% vs. 81%， P=0.003），因此符合优势标准。DTG-ABC-3TC组达到病毒抑制的中位时间比EFV-TDF-FTC组短(28天比84天，P
BackgroundDolutegravir (S/GSK1349572), a once-daily, unboosted integrase inhibitor, was recently approved in the United States for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in combination with other antiretroviral agents. Dolutegravir, in combination with abacavir-lamivudine, may provide a simplified regimen.MethodsWe conducted a randomized, double-blind, phase 3 study involving adult participants who had not received previous therapy for HIV-1 infection and who had an HIV-1 RNA level of 1000 copies per milliliter or more. Participants were randomly assigned to dolutegravir at a dose of 50 mg plus abacavir-lamivudine once daily (DTG-ABC-3TC group) or combination therapy with efavirenz-tenofovir disoproxil fumarate (DF)-emtricitabine once daily (EFV-TDF-FTC group). The primary end point was the proportion of participants with an HIV-1 RNA level of less than 50 copies per milliliter at week 48. Secondary end points included the time to viral suppression, the change from baseline in CD4+ T-cell count, safety, and viral resistance.ResultsA total of 833 participants received at least one dose of study drug. At week 48, the proportion of participants with an HIV-1 RNA level of less than 50 copies per milliliter was significantly higher in the DTG-ABC-3TC group than in the EFV-TDF-FTC group (88% vs. 81%, P=0.003), thus meeting the criterion for superiority. The DTG-ABC-3TC group had a shorter median time to viral suppression than did the EFV-TDF-FTC group (28 vs. 84 days, P