多替拉韦加利伟与依非韦伦加利伟作为 HIV 感染者的初始抗逆转录病毒治疗：系统评价。

Dolutegravir Plus Two Nucleoside Reverse Transcriptase Inhibitors versus Efavirenz Plus Two Nucleoside Reverse Transcriptase Inhibitors As Initial Antiretroviral Therapy for People with HIV: A Systematic Review.

机构信息

Global Health Sciences, University of California, San Francisco, San Francisco, California, United States of America.

出版信息

PLoS One. 2016 Oct 13;11(10):e0162775. doi: 10.1371/journal.pone.0162775. eCollection 2016.

BACKGROUND

Dolutegravir (DTG) is a once-daily unboosted second-generation integrase-inhibitor that along with two nucleoside reverse transcriptase inhibitors is one of several regimens recommended by the United States, United Kingdom and European Union for first-line antiretroviral treatment of people with HIV infection. Our objective was to review the evidence for the efficacy and safety of DTG-based first-line regimens compared to efavirenz (EFV)-based regimens.

METHODS

We conducted a systematic review. We comprehensively searched a range of databases as well as conference abstracts and a trials registry. We used Cochrane methods in screening and data collection and assessed each study's risk of bias with the Cochrane tool. We meta-analyzed data using a fixed-effects model. We used GRADE to assess evidence quality.

RESULTS

From 492 search results, we identified two randomized controlled trials, reported in five peer-reviewed articles and one conference abstract. One trial tested two DTG-based regimens (DTG + abacavir (ABC) + lamivudine (3TC) or DTG + tenofovir + emtricitabine) against an EFV-based regimen (EFV+ ABC+3TC). The other trial tested DTG+ABC+3TC against EFV+ABC+3TC. In meta-analysis, DTG-containing regimens were superior to EFV-containing regimens at 48 weeks and at 96 weeks (RR = 1.10, 95% CI 1.04-1.16; and RR = 1.12, 95% CI 1.04-1.21, respectively). In one trial, the DTG-containing regimen was superior at 144 weeks (RR = 1.13, 95% CI 1.02-1.24). DTG-containing regimens were superior in reducing treatment discontinuation compared to those containing EFV at 96 weeks and at 144 weeks (RR = 0.27, 95% CI 0.15-0.50; and RR = 0.28, 95% CI 0.16-0.48, respectively). Risk of serious adverse events was similar in each regimen at 96 weeks (RR = 1.15, 95% CI 0.80-1.63) and 144 weeks (RR = 0.93, 95% CI 0.68-1.29). Risk of bias was moderate overall, as was GRADE evidence quality.

CONCLUSIONS

DTG-based regimens should be considered in future World Health Organization guidelines for initial HIV treatment.

背景

多替拉韦（DTG）是一种每日一次的非增强型第二代整合酶抑制剂，与两种核苷逆转录酶抑制剂联合使用，是美国、英国和欧盟推荐的几种一线抗艾滋病毒治疗方案之一，适用于艾滋病毒感染者。我们的目的是评估基于 DTG 的一线方案与基于依非韦伦（EFV）的方案相比的疗效和安全性证据。

方法

我们进行了系统评价。我们全面搜索了一系列数据库以及会议摘要和试验注册处。我们使用 Cochrane 方法进行筛选和数据收集，并使用 Cochrane 工具评估每个研究的偏倚风险。我们使用固定效应模型对数据进行荟萃分析。我们使用 GRADE 评估证据质量。

结果

从 492 条搜索结果中，我们确定了两项随机对照试验，分别在五篇同行评议的文章和一篇会议摘要中报道。一项试验比较了两种基于 DTG 的方案（DTG+阿巴卡韦（ABC）+拉米夫定（3TC）或 DTG+替诺福韦+恩曲他滨）与基于 EFV 的方案（EFV+ABC+3TC）。另一项试验比较了 DTG+ABC+3TC 与 EFV+ABC+3TC。荟萃分析显示，在 48 周和 96 周时，含 DTG 的方案优于含 EFV 的方案（RR=1.10，95%CI 1.04-1.16；RR=1.12，95%CI 1.04-1.21）。在一项试验中，含 DTG 的方案在 144 周时更优（RR=1.13，95%CI 1.02-1.24）。在 96 周和 144 周时，与含 EFV 的方案相比，含 DTG 的方案在减少治疗停药方面更具优势（RR=0.27，95%CI 0.15-0.50；RR=0.28，95%CI 0.16-0.48）。在 96 周（RR=1.15，95%CI 0.80-1.63）和 144 周（RR=0.93，95%CI 0.68-1.29）时，每个方案的严重不良事件风险相似。总体而言，偏倚风险和 GRADE 证据质量均为中度。