Once-daily dolutegravir versus darunavir plus ritonavir for treatment-naive adults with HIV-1 infection (FLAMINGO): 96 week results from a randomised, open-label, phase 3b study
Once-daily dolutegravir versus darunavir plus ritonavir for treatment-naive adults with HIV-1 infection (FLAMINGO): 96 week results from a randomised, open-label, phase 3b study
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DOI：
10.1016/s2352-3018(15)00027-2
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发表时间：
2015-04-01
期刊：
影响因子：
16.1
通讯作者：
Brennan, Clare
中科院分区：
文献类型：
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作者：
Molina, Jean-Michel;Clotet, Bonaventura;Brennan, Clare
背景FLAMINGO研究48周的初步分析显示，每天服用一次度鲁特韦的患者的病毒学应答率明显高于每天服用一次利托那韦加强的达鲁纳韦的患者，且耐受性相似。我们在96周时分析了次要疗效和安全性结果。方法FLAMINGO是一项多中心、开放标签、3b期、非劣效性研究，研究对象为HIV-1感染初治成人。患者被随机分配（1：1）至度鲁特韦50 mg或地瑞那韦800 mg加利托那韦100 mg，并选择替诺福韦和恩曲他滨联合治疗或阿巴卡韦和拉米夫定联合背景治疗。主要终点是血浆HIV-1 RNA低于50拷贝/mL和安全性。非劣效性界值为-12%。如果95%CI的下限大于0%，则我们得出结论，度鲁特韦优于利托那韦加强的地瑞那韦。该试验在www.example.com注册，编号NCT 01449929。结果在筛选的595名患者中，488名被随机分配，484名被纳入分析（242名被分配接受dolutegravir，242名被分配接受利托那韦加强的darunavir）。在96周时，度鲁特韦组242名患者中有194名（80%）和利托那韦加强的达芦那韦组242名患者中有164名（68%）的HIV-1 RNA低于50拷贝/mL（校正差异12.4，95% CI 4.7 - 20.2; p = 0.002），基线时病毒载量高的患者差异最大（50/61 [82%] vs 32/61 [52%]，同质性检验p = 0.014）。dolutegravir组中有6名参与者（48周后有3名参与者），darunavir + ritonavir组中有13名参与者（4名）因不良事件而停药。最常见的药物相关不良事件是腹泻（度鲁特韦组23/242 [10%] vs地瑞那韦+利托那韦组57/242 [24%]），恶心（31/242 [13%] vs 34/242 [14%]），和头痛（17/242 [7%] vs 12/242 [5%]）。解释每日一次dolutegravir比每日一次利托那韦具有更高的病毒学应答率。注射了达芦那韦对于HIV-1感染的初治患者，度鲁特韦在疗效和安全性方面优于加强的达芦那韦方案和核苷逆转录酶抑制剂背景治疗。
Background The primary analysis of the FLAMINGO study at 48 weeks showed that patients taking dolutegravir once daily had a significantly higher virological response rate than did those taking ritonavir-boosted darunavir once daily, with similar tolerability. We present secondary efficacy and safety results analysed at 96 weeks.Methods FLAMINGO was a multicentre, open-label, phase 3b, non-inferiority study of HIV-1-infected treatmentnaive adults. Patients were randomly assigned (1:1) to dolutegravir 50 mg or darunavir 800 mg plus ritonavir 100 mg, with investigator-selected combination tenofovir and emtricitabine or combination abacavir and lamivudine background treatment. The main endpoints were plasma HIV-1 RNA less than 50 copies per mL and safety. The non-inferiority margin was -12%. If the lower end of the 95% CI was greater than 0%, then we concluded that dolutegravir was superior to ritonavir-boosted darunavir. This trial is registered with ClinicalTrials.gov, number NCT01449929.Findings Of 595 patients screened, 488 were randomly assigned and 484 included in the analysis (242 assigned to receive dolutegravir and 242 assigned to receive ritonavir-boosted darunavir). At 96 weeks, 194 (80%) of 242 patients in the dolutegravir group and 164 (68%) of 242 in the ritonavir-boosted darunavir group had HIV-1 RNA less than 50 copies per mL (adjusted difference 12.4, 95% CI 4.7-20.2; p=0.002), with the greatest difference in patients with high viral load at baseline (50/61 [82%] vs 32/61 [52%], homogeneity test p=0.014). Six participants (three since 48 weeks) in the dolutegravir group and 13 (four) in the darunavir plus ritonavir group discontinued because of adverse events. The most common drug-related adverse events were diarrhoea (23/242 [10%] in the dolutegravir group vs 57/242 [24%] in the darunavir plus ritonavir group), nausea (31/242 [13%] vs 34/242 [14%]), and headache (17/242 [7%] vs 12/242 [5%]).Interpretation Once-daily dolutegravir is associated with a higher virological response rate than is once-daily ritonavir-boosted darunavir. Dolutegravir compares favourably in efficacy and safety to a boosted darunavir regimen with nucleoside reverse transcriptase inhibitor background treatment for HIV-1-infected treatment-naive patients.