Centre for Applied Medical Research, St Vincent's Hospital.
University of New South Wales, Sydney, Australia.
AIDS. 2019 Mar 1;33(3):443-453. doi: 10.1097/QAD.0000000000002077.
We updated a prior systematic review of initial antiretroviral therapy (ART) efficacy through week 144.
Studies (1994 to July 2017) were drawn from PubMed, ClinicalTrials.gov, Cochrane Library, and major conferences; design, eligibility, patient, and ART data were abstracted. Outcomes are expressed as group size-weighted means. Mixed-effects meta-regression was used to identify sources of efficacy heterogeneity.
Within 354 groups (181 studies, 77 999 participants), principal backbones were tenofovir-emtricitabine (TDF/TAF-FTC) (44.2%), thymidine-based (27.7%), and abacavir-lamivudine (9.7%). Principal anchors were non-nucleoside analog (49.7%), boosted protease inhibitor (28.1%), and integrase inhibitor (INSTI; 11.5%). Mean intention-to-treat efficacy (RNA <50 copies/ml) was 71.3%, 63.5% (145 groups), and 61.8% (48 groups) at weeks 48, 96, and 144, respectively (for post-2010 studies, 83.8%, 79.9%, and 77.1%). TDF/TAF-FTC and INSTI were independent predictors of greater efficacy at weeks 48, 96, and 144. Additional independent predictors at week 48 were pre-ART resistance genotyping, higher baseline CD4 cell count, and once-daily ART. Fewer pills per day predicted greater efficacy at weeks 96 and 144. Phase 4 studies yielded progressively inferior efficacy than phase 3 studies (difference 5.1% at week 48, 15.8% at week 144). Cessation through week 144 overall (29.4%) and for adverse events (8.9%) declined over time, but cessation for virological failure (5.2%) did not.
Initial ART efficacy continues to improve, but more than 20% of post-2010 patients failed over 3 years. Real-world efficacy is lower than in phase 3 trials. Guidelines should list non-INSTI-based initial ART as nonpreferred. Strategies are needed to improve access to pre-ART genotyping and to increase early initiation of once-daily ART.
我们更新了之前关于初始抗逆转录病毒治疗（ART）疗效的系统评价，截至第 144 周。
研究（1994 年至 2017 年 7 月）来自 PubMed、ClinicalTrials.gov、Cochrane 图书馆和主要会议；设计、资格、患者和 ART 数据被提取出来。结果表示为群体大小加权平均值。混合效应元回归用于确定疗效异质性的来源。
在 354 个组（181 项研究，77999 名参与者）中，主要骨干是替诺福韦-恩曲他滨（TDF/TAF-FTC）（44.2%）、基于胸苷的药物（27.7%）和阿巴卡韦-拉米夫定（9.7%）。主要的锚定物是非核苷类似物（49.7%）、增效蛋白酶抑制剂（28.1%）和整合酶抑制剂（INSTI；11.5%）。按意向治疗（RNA<50 拷贝/ml）计算，第 48、96 和 144 周的疗效分别为 71.3%、63.5%（145 组）和 61.8%（48 组）（对于 2010 年后的研究，分别为 83.8%、79.9%和 77.1%）。TDF/TAF-FTC 和 INSTI 是第 48、96 和 144 周疗效的独立预测因素。第 48 周时，另外的独立预测因素还有 ART 前耐药基因分型、较高的基线 CD4 细胞计数和每日一次的 ART。每天服用的药丸越少，第 96 和 144 周的疗效就越好。第 4 期研究的疗效劣于第 3 期研究（第 48 周时差异为 5.1%，第 144 周时差异为 15.8%）。第 144 周时，总的停药率（29.4%）和因不良事件停药率（8.9%）随时间下降，但因病毒学失败停药率（5.2%）并未下降。
初始 ART 的疗效仍在不断提高，但超过 20%的 2010 年后患者在 3 年内失败。实际疗效低于 3 期试验。指南应将非 INSTI 为基础的初始 ART 列为非首选。需要采取策略，以改善获得 ART 前基因分型的机会，并增加每日一次的 ART 的早期启动。
