IrsiCaixa, Hospital Universitari "Germans Trias i Pujol", Badalona, UAB, Universitat de Vic, Catalonia, Spain.
University of Cincinnati, Cincinnati, OH, USA.
Lancet. 2014 Jun 28;383(9936):2222-31. doi: 10.1016/S0140-6736(14)60084-2. Epub 2014 Apr 1.
Dolutegravir has been shown to be non-inferior to an integrase inhibitor and superior to a non-nucleoside reverse transcriptase inhibitor (NNRTI). In FLAMINGO, we compared dolutegravir with darunavir plus ritonavir in individuals naive for antiretroviral therapy.
In this multicentre, open-label, phase 3b, non-inferiority study, HIV-1-infected antiretroviral therapy-naive adults with HIV-1 RNA concentration of 1000 copies per mL or more and no resistance at screening were randomly assigned (1:1) to receive either dolutegravir 50 mg once daily or darunavir 800 mg plus ritonavir 100 mg once daily, with investigator-selected tenofovir-emtricitabine or abacavir-lamivudine. Randomisation was stratified by screening HIV-1 RNA (≤100,000 or >100,000 copies per mL) and nucleoside reverse transcriptase inhibitor (NRTI) selection. The primary endpoint was the proportion of patients with HIV-1 RNA concentration lower than 50 copies per mL (Food and Drug Administration [FDA] snapshot algorithm) at week 48 with a 12% non-inferiority margin. This trial is registered with ClinicalTrials.gov, NCT01449929.
Recruitment began on Oct 31, 2011, and was completed on May 24, 2012, in 64 research centres in nine countries worldwide. Of 595 patients screened, 484 patients were included in the analysis (242 in each group). At week 48, 217 (90%) patients receiving dolutegravir and 200 (83%) patients receiving darunavir plus ritonavir had HIV-1 RNA of less than 50 copies per mL (adjusted difference 7·1%, 95% CI 0·9-13·2), non-inferiority and on pre-specified secondary analysis dolutegravir was superior (p=0·025). Confirmed virological failure occurred in two (<1%) patients in each group; we recorded no treatment-emergent resistance in either group. Discontinuation due to adverse events or stopping criteria was less frequent for dolutegravir (four [2%] patients) than for darunavir plus ritonavir (ten [4%] patients) and contributed to the difference in response rates. The most commonly reported (≥10%) adverse events were diarrhoea (dolutegravir 41 [17%] patients vs darunavir plus ritonavir 70 [29%] patients), nausea (39 [16%] vs 43 [18%]), and headache (37 [15%] vs 24 [10%]). Patients receiving dolutegravir had significantly fewer low-density lipoprotein values of grade 2 or higher (11 [2%] vs 36 [7%]; p=0·0001).
Once-daily dolutegravir was superior to once-daily darunavir plus ritonavir. Once-daily dolutegravir in combination with fixed-dose NRTIs represents an effective new treatment option for HIV-1-infected, treatment-naive patients.
ViiV Healthcare and Shionogi & Co.
多替拉韦已被证明在非劣效于整合酶抑制剂的基础上优于非核苷类逆转录酶抑制剂（NNRTI）。在 FLAMINGO 中，我们比较了多替拉韦与达芦那韦加利托那韦在从未接受过抗逆转录病毒治疗的个体中的疗效。
在这项多中心、开放性标签、3b 期非劣效性研究中，HIV-1 RNA 浓度为 1000 拷贝/毫升或更高且筛选时无耐药性的 HIV-1 感染、初次接受抗逆转录病毒治疗的成人患者，被随机分配（1:1）接受每日一次 50 毫克多替拉韦或每日一次 800 毫克达芦那韦加利托那韦，联合研究者选择的替诺福韦-恩曲他滨或阿巴卡韦-拉米夫定。随机分组按筛选时的 HIV-1 RNA（≤100000 或 >100000 拷贝/毫升）和核苷逆转录酶抑制剂（NRTI）选择分层。主要终点是第 48 周时 HIV-1 RNA 浓度低于 50 拷贝/毫升（食品和药物管理局[FDA]快照算法）的患者比例，非劣效性边界为 12%。这项试验在 ClinicalTrials.gov 上注册，编号为 NCT01449929。
招募于 2011 年 10 月 31 日开始，于 2012 年 5 月 24 日在全球九个国家的 64 个研究中心完成。在 595 名筛选的患者中，有 484 名患者纳入分析（每组 242 名）。第 48 周时，217 名（90%）接受多替拉韦的患者和 200 名（83%）接受达芦那韦加利托那韦的患者 HIV-1 RNA 小于 50 拷贝/毫升（调整差异 7.1%，95%CI 0.9-13.2），具有非劣效性，在预先指定的次要分析中，多替拉韦具有优越性（p=0.025）。两组各有两名（<1%）患者发生确认的病毒学失败；我们在两组中均未记录到治疗后出现的耐药性。因不良反应或停药标准而停药的患者在多替拉韦组（4 名[2%]）少于达芦那韦加利托那韦组（10 名[4%]），这导致了两组间的应答率差异。最常见（≥10%）的不良反应是腹泻（多替拉韦组 41 名[17%]患者 vs 达芦那韦加利托那韦组 70 名[29%]患者）、恶心（39 名[16%] vs 43 名[18%]）和头痛（37 名[15%] vs 24 名[10%]）。接受多替拉韦治疗的患者低密度脂蛋白值为 2 级或更高的明显较少（11 名[2%] vs 36 名[7%]；p=0.0001）。
每日一次的多替拉韦优于每日一次的达芦那韦加利托那韦。每日一次的多替拉韦联合固定剂量 NRTIs 为 HIV-1 感染、初次接受治疗的患者提供了一种有效的新治疗选择。
ViiV 医疗保健公司和盐野义制药公司。
