48-week efficacy and safety of dolutegravir relative to commonly used third agents in treatment-naive HIV-1-infected patients: a systematic review and network meta-analysis.
48-week efficacy and safety of dolutegravir relative to commonly used third agents in treatment-naive HIV-1-infected patients: a systematic review and network meta-analysis.
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DOI：
10.1371/journal.pone.0105653
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Nichols G
中科院分区：
文献类型：
--
作者：
Patel DA;Snedecor SJ;Tang WY;Sudharshan L;Lim JW;Cuffe R;Pulgar S;Gilchrist KA;Camejo RR;Stephens J;Nichols G
网络荟萃分析可以提供在头对头随机对照试验中未直接研究的治疗方法的相对疗效估计。我们评估了dolutegravir （DTG）与目前指南推荐的第三种药物的相对疗效和安全性，包括利托那韦增强的阿他那韦（ATV/r），利托那韦增强的达那韦（DRV/r），依非韦伦（EFV）， cobicistat增强的elvittegravir (EVG/c)，利托那韦增强的洛匹那韦（LPV/r），雷替格拉韦（RAL）和利匹韦林（RPV），用于初次治疗的hiv -1感染患者。对已发表的文献进行了系统回顾，以确定3/4期随机对照临床试验（截至2013年8月），包括至少三分之一的感兴趣药物与主干核苷逆转录酶抑制剂（NRTI）方案联合使用。采用贝叶斯固定效应网络meta分析模型调整核苷类逆转录酶抑制剂（富马酸替诺福韦二oproxil /emtricitabine [TDF/FTC]或阿巴卡韦/拉米夫定[ABC/3TC]）类型，评估与所有其他治疗相比，DTG第48周的疗效（HIV-RNA抑制至<50拷贝/mL， CD4+细胞变化/µL）和安全性（脂质变化、不良事件和因不良事件而停药）。进行敏感性分析，评估NRTI治疗调整和随机效应模型的影响。包括17000名患者在内的31项研究被纳入分析。调整NRTI主干的作用，与ATV/r、DRV/r、EFV、LPV/r和RPV相比，DTG治疗导致病毒学抑制的几率显著增加（HIV RNA<50拷贝/mL）， CD4+细胞/µL增加。与所有治疗相比，多替格拉韦在总胆固醇、低密度脂蛋白、甘油三酯方面的变化更好或相当，不良事件和因不良事件而停药的几率更低。随机效应和未调整的模型得出了类似的结论。在hiv -1感染的初次治疗患者中，DTG的三项临床试验证明其疗效和安全性与DRV、RAL和EFV相当或更好。该网络荟萃分析表明，DTG也优于或可与其他常用的第三方药物（ATV/r、LPV/r、RPV和EVG/c）相媲美。
A network meta-analysis can provide estimates of relative efficacy for treatments not directly studied in head-to-head randomized controlled trials. We estimated the relative efficacy and safety of dolutegravir (DTG) versus third agents currently recommended by guidelines, including ritonavir-boosted atazanavir (ATV/r), ritonavir-boosted darunavir (DRV/r), efavirenz (EFV), cobicistat-boosted elvitegravir (EVG/c), ritonavir-boosted lopinavir (LPV/r), raltegravir (RAL), and rilpivirine (RPV), in treatment-naive HIV-1–infected patients. A systematic review of published literature was conducted to identify phase 3/4 randomized controlled clinical trials (up to August 2013) including at least one third agent of interest in combination with a backbone nucleoside reverse transcriptase inhibitor (NRTI) regimen. Bayesian fixed-effect network meta-analysis models adjusting for the type of nucleoside reverse transcriptase inhibitor backbone (tenofovir disoproxil fumarate/emtricitabine [TDF/FTC] or abacavir/lamivudine [ABC/3TC]) were used to evaluate week 48 efficacy (HIV-RNA suppression to <50 copies/mL and change in CD4+ cells/µL) and safety (lipid changes, adverse events, and discontinuations due to adverse events) of DTG relative to all other treatments. Sensitivity analyses assessing the impact of NRTI treatment adjustment and random-effects models were performed. Thirty-one studies including 17,000 patients were combined in the analysis. Adjusting for the effect of NRTI backbone, treatment with DTG resulted in significantly higher odds of virologic suppression (HIV RNA<50 copies/mL) and increase in CD4+ cells/µL versus ATV/r, DRV/r, EFV, LPV/r, and RPV. Dolutegravir had better or equivalent changes in total cholesterol, LDL, triglycerides, and lower odds of adverse events and discontinuation due to adverse events compared to all treatments. Random-effects and unadjusted models resulted in similar conclusions. Three clinical trials of DTG have demonstrated comparable or superior efficacy and safety to DRV, RAL, and EFV in HIV-1–infected treatment-naive patients. This network meta-analysis suggests DTG is also favorable or comparable to other commonly used third agents (ATV/r, LPV/r, RPV, and EVG/c).
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影响因子：
11.8
作者：
DeJesus, E;Herrera, G;Scott, TR
通讯作者：
Scott, TR
DOI：
10.1111/j.1742-1241.2011.02807.x
发表时间：
2011-12-01
影响因子：
2.6
作者：
DeJesus, E.;Mills, A.;Storfer, S.
通讯作者：
Storfer, S.
DOI：
10.1177/0272989x13485155
发表时间：
2013-07
期刊：
Medical decision making : an international journal of the Society for Medical Decision Making
影响因子：
--
作者：
Dias S;Welton NJ;Sutton AJ;Ades AE
通讯作者：
Ades AE
影响因子：
1.5
作者：
Aberg, Judith A.;Tebas, Pablo;De La Rosa, Guy
通讯作者：
De La Rosa, Guy
影响因子：
168.9
作者：
DeJesus, Edwin;Rockstroh, Juergen K.;Kearney, Brian P.
通讯作者：
Kearney, Brian P.