Once-daily dolutegravir versus raltegravir in antiretroviral-naive adults with HIV-1 infection: 48 week results from the randomised, double-blind, non-inferiority SPRING-2 study
Once-daily dolutegravir versus raltegravir in antiretroviral-naive adults with HIV-1 infection: 48 week results from the randomised, double-blind, non-inferiority SPRING-2 study
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DOI：
10.1016/s0140-6736(12)61853-4
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发表时间：
2013-03-02
期刊：
影响因子：
168.9
通讯作者：
Min, Sherene
中科院分区：
文献类型：
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作者：
Raffi, Francois;Rachlis, Anita;Min, Sherene
背景Dolutegravir（S/GSK 1349572）是一种每日一次的HIV整合酶抑制剂，具有强效抗病毒活性和良好的安全性。我们比较了度鲁特韦与HIV整合酶抑制剂雷特格韦作为HIV-1成人患者的初始治疗。方法SPRING-2是一项为期96周、3期、随机、双盲、活性对照、非劣效性研究，于2010年10月19日开始，在加拿大、美国、澳大利亚和欧洲的100个地点进行。HIV-1感染且HIV-1 RNA浓度≥ 1000拷贝/mL的初治成人（年龄≥ 18岁）通过计算机生成的随机序列随机分配（1：1）接受度鲁特韦（50 mg，每日一次）或雷特格韦（400 mg，每日两次）。研究药物与替诺福韦/恩曲他滨或阿巴卡韦/拉米夫定联合给药。通过筛选HIV-1 RNA（100 000拷贝/mL）和核苷逆转录酶抑制剂骨架对随机化进行分层。随机化前，研究者未对HIV-1 RNA结果设盲。主要终点是48周时HIV-1 RNA低于50拷贝/mL的受试者比例，非劣效性界值为10%。主要次要终点是CD 4细胞计数较基线的变化、不良事件的发生率和严重程度、实验室参数的变化以及耐药的基因型或表型证据。我们的主要分析是通过意向治疗。该试验注册于ClinicalTrials.gov，编号NCT 01227824。结果411例患者随机分配接受dolutegravir和411例接受raltegravir，并接受至少一剂研究药物。在48周时，度鲁特韦组有361例（88%）患者的HIV-1 RNA值低于50拷贝/mL，而雷特格韦组有351例（85%）（校正差异2.5%; 95% CI -2.2至7.1）。治疗组之间的不良事件相似。最常见的事件是恶心（度鲁特韦组59例[14%]患者vs雷特格韦组53例[13%]患者）、头痛（51例[12%] vs 48例[12%]）、鼻咽炎（46例[11%] vs 48例[12%]）和腹泻（每组47例[11%]）。很少有患者发生药物相关的严重不良事件（3例[
Background Dolutegravir (S/GSK1349572) is a once-daily HIV integrase inhibitor with potent antiviral activity and a favourable safety profile. We compared dolutegravir with HIV integrase inhibitor raltegravir, as initial treatment for adults with HIV-1.Methods SPRING-2 is a 96 week, phase 3, randomised, double-blind, active-controlled, non-inferiority study that began on Oct 19, 2010, at 100 sites in Canada, USA, Australia, and Europe. Treatment-naive adults (aged >= 18 years) with HIV-1 infection and HIV-1 RNA concentrations of 1000 copies per mL or greater were randomly assigned (1: 1) via a computer-generated randomisation sequence to receive either dolutegravir (50 mg once daily) or raltegravir (400 mg twice daily). Study drugs were given with coformulated tenofovir/emtricitabine or abacavir/lamivudine. Randomisation was stratified by screening HIV-1 RNA (100 000 copies per mL) and nucleoside reverse transcriptase inhibitor backbone. Investigators were not masked to HIV-1 RNA results before randomisation. The primary endpoint was the proportion of participants with HIV-1 RNA less than 50 copies per mL at 48 weeks, with a 10% non-inferiority margin. Main secondary endpoints were changes from baseline in CD4 cell counts, incidence and severity of adverse events, changes in laboratory parameters, and genotypic or phenotypic evidence of resistance. Our primary analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01227824.Findings 411 patients were randomly allocated to receive dolutegravir and 411 to receive raltegravir and received at least one dose of study drug. At 48 weeks, 361 (88%) patients in the dolutegravir group achieved an HIV-1 RNA value of less than 50 copies per mL compared with 351 (85%) in the raltegravir group (adjusted difference 2.5%; 95% CI -2.2 to 7.1). Adverse events were similar between treatment groups. The most common events were nausea (59 [14%] patients in the dolutegravir group vs 53 [13%] in the raltegravir group), headache (51 [12%] vs 48 [12%]), nasopharyngitis (46 [11%] vs 48 [12%]), and diarrhoea (47 [11%] in each group). Few patients had drug-related serious adverse events (three [