Clinical use of HIV integrase inhibitors: a systematic review and meta-analysis.
Clinical use of HIV integrase inhibitors: a systematic review and meta-analysis.
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DOI：
10.1371/journal.pone.0052562
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Vandekerckhove L
中科院分区：
文献类型：
--
作者：
Messiaen P;Wensing AM;Fun A;Nijhuis M;Brusselaers N;Vandekerckhove L
抗逆转录病毒治疗的最佳方案选择是获得长期临床成功的关键。整合酶抑制剂已被迅速采用，作为目前抗逆转录病毒治疗方案的一部分。本研究的目的是审查整合酶抑制剂在临床环境中使用的证据。从2006年4月至2012年11月，筛选了MEDLINE和Web of Science，以及手工检索的科学会议记录。多位评审员独立筛选了1323篇引文，以确定临床实践中整合酶抑制剂使用的随机对照试验、非随机对照试验和队列研究。进行了独立的重复数据提取和质量评估。纳入了48项关于整合酶抑制剂在未经抗逆转录病毒治疗的患者和病毒学失败或在病毒学抑制时改用整合酶抑制剂的治疗经验丰富的患者中使用的独特研究。在具有可比结局指标和适应症的选定研究（n = 16）中，基于改良的意向治疗（mITT）、治疗中（OT）和治疗后（AT）病毒学结局数据进行荟萃分析。 在初治患者中，观察到基于整合酶受体的方案的优势比（OR）有利（mITT OR 0.71，95% CI 0.59-0.86）。然而，整合酶抑制剂与蛋白酶抑制剂的组合并没有导致明显更好的病毒学结果。证据进一步支持病毒学失败后使用整合酶抑制剂（mITT OR 0.27; 95% CI 0.11-0.66），但不支持在成功治疗期间从高遗传屏障药物转换为整合酶抑制剂（mITT OR 1.43; 95% CI 0.89-2.31）。与其他方案相比，基于整合酶通道的方案产生类似的免疫应答。对于雷特格韦和埃替格韦，观察到耐药性发展的遗传屏障较低，但对于度鲁特韦则没有。在一线治疗中，整合酶抑制剂上级优于其他方案。整合酶抑制剂在病毒学失败后的使用也得到了荟萃分析的支持。然而，当在治疗经验丰富的患者中更换高遗传屏障药物时，需要谨慎使用。
Optimal regimen choice of antiretroviral therapy is essential to achieve long-term clinical success. Integrase inhibitors have swiftly been adopted as part of current antiretroviral regimens. The purpose of this study was to review the evidence for integrase inhibitor use in clinical settings. MEDLINE and Web-of-Science were screened from April 2006 until November 2012, as were hand-searched scientific meeting proceedings. Multiple reviewers independently screened 1323 citations in duplicate to identify randomized controlled trials, nonrandomized controlled trials and cohort studies on integrase inhibitor use in clinical practice. Independent, duplicate data extraction and quality assessment were conducted. 48 unique studies were included on the use of integrase inhibitors in antiretroviral therapy-naive patients and treatment-experienced patients with either virological failure or switching to integrase inhibitors while virologically suppressed. On the selected studies with comparable outcome measures and indication (n = 16), a meta-analysis was performed based on modified intention-to-treat (mITT), on-treatment (OT) and as-treated (AT) virological outcome data. In therapy-naive patients, favorable odds ratios (OR) for integrase inhibitor-based regimens were observed, (mITT OR 0.71, 95% CI 0.59–0.86). However, integrase inhibitors combined with protease inhibitors only did not result in a significant better virological outcome. Evidence further supported integrase inhibitor use following virological failure (mITT OR 0.27; 95% CI 0.11–0.66), but switching to integrase inhibitors from a high genetic barrier drug during successful treatment was not supported (mITT OR 1.43; 95% CI 0.89–2.31). Integrase inhibitor-based regimens result in similar immunological responses compared to other regimens. A low genetic barrier to drug-resistance development was observed for raltegravir and elvitegravir, but not for dolutegravir. In first-line therapy, integrase inhibitors are superior to other regimens. Integrase inhibitor use after virological failure is supported as well by the meta-analysis. Careful use is however warranted when replacing a high genetic barrier drug in treatment-experienced patients switching successful treatment.