Baril J, Conway B, Giguère P, Ferko N, Hollmann S, Angel J B
Hospital of the University of Montreal, Montréal, QC, Canada.
HIV Med. 2014 May;15(5):301-10. doi: 10.1111/hiv.12118. Epub 2013 Dec 9.
Treatment simplification involving induction with a ritonavir (RTV)-boosted protease inhibitor (PI) replaced by a nonboosted PI (i.e. atazanavir) has been shown to be a viable option for long-term antiretroviral therapy. To evaluate the clinical evidence for this approach, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating efficacy and safety in patients with established virological suppression.
Several databases were searched without limits on time or language. Searches of conferences were also conducted. RCTs were included if they compared a PI/RTV regimen to unboosted atazanavir, after induction with PI/RTV. The meta-analysis was conducted using a random effects model for the proportion achieving virological suppression (i.e. HIV RNA < 50 and <400 HIV-1 RNA copies/mL), CD4 cell counts, lipid levels and liver function tests. Dichotomous outcomes were reported as risk ratios (RRs) and continuous outcomes as mean differences (MDs).
Five studies (n = 1249) met the inclusion criteria. The meta-analysis demonstrated no statistically significant difference in efficacy (i.e. HIV RNA < 50 copies/mL) between PI/RTV and unboosted atazanavir [RR = 1.04; 95% confidence interval (CI) 0.99 to 1.10], with no heterogeneity. Findings were similar in a subanalysis of studies where atazanavir/RTV was the only PI/RTV used during induction. Additional efficacy results support these findings. A significant reduction in total cholesterol (P < 0.00001), triglycerides (P = 0.0002), low-density lipoprotein (LDL) cholesterol (P = 0.009) and hyperbilirubinaemia (P = 0.02) was observed with unboosted atazanavir vs. PI/RTV.
The meta-analysis demonstrated that switching patients with virological suppression from an RTV-boosted PI to unboosted atazanavir leads to improvements in safety (i.e. blood parameter abnormalities) without sacrificing virological efficacy.
已证明，对于长期抗逆转录病毒治疗而言，将包含利托那韦（RTV）增强型蛋白酶抑制剂（PI）诱导治疗替换为非增强型PI（即阿扎那韦）的简化治疗是一种可行的选择。为评估这种治疗方法的临床证据，我们对评估病毒学已得到抑制的患者的疗效和安全性的随机对照试验（RCT）进行了系统评价和荟萃分析。
检索了多个数据库，对时间或语言均无限制。还检索了会议资料。纳入的RCT需为在使用PI/RTV诱导治疗后，将PI/RTV方案与非增强型阿扎那韦进行比较的研究。荟萃分析采用随机效应模型，用于分析实现病毒学抑制（即HIV RNA<50和<400拷贝/mL）、CD4细胞计数、血脂水平和肝功能检查的比例。二分法结局以风险比（RR）报告，连续型结局以平均差（MD）报告。
五项研究（n = 1249）符合纳入标准。荟萃分析表明，PI/RTV与非增强型阿扎那韦在疗效（即HIV RNA<50拷贝/mL）方面无统计学显著差异[RR = 1.04；95%置信区间（CI）0.99至1.10]，且无异质性。在阿扎那韦/RTV是诱导治疗期间唯一使用的PI/RTV的研究亚组分析中，结果相似。其他疗效结果也支持这些发现。与PI/RTV相比，非增强型阿扎那韦可使总胆固醇（P<0.00001）、甘油三酯（P = 0.0002）、低密度脂蛋白（LDL）胆固醇（P = 0.009）和高胆红素血症（P = 0.02）显著降低。
荟萃分析表明，将病毒学已得到抑制的患者从RTV增强型PI转换为非增强型阿扎那韦可在不牺牲病毒学疗效的情况下提高安全性（即血液参数异常情况）。
