Efficacy of Initial Antiretroviral Therapy for HIV-1 Infection in Adults: A Systematic Review and Meta-Analysis of 114 Studies with up to 144 Weeks' Follow-Up

BackgroundA comprehensive assessment of initial HIV-1 treatment success may inform study design and treatment guidelines.MethodsGroup-based, systematic review and meta-analysis of initial antiretroviral therapy studies, in adults, of ≥48 weeks duration, reported through December 31, 2012. Size-weighted, intention-to-treat efficacy was calculated. Parameters of study design/eligibility, participant and treatment characteristics were abstracted. Multivariable, random effects, linear regression models with backwards, stepwise selection were then used to identify variables associated with efficacy.Outcome MeasuresAntiviral efficacy (undetectable plasma viral load) and premature cessation of therapy.Results114 studies were included (216 treatment groups; 40,124 participants; mean CD4 count 248 cells/µL [SD 81]; mean HIV-1 plasma viral load log10 4.9 [SD 0.2]). Mean efficacy across all groups was 60% (SD 16) over a mean 82 weeks' follow-up (SD 38). Efficacy declined over time: 66% (SD 16) at 48 weeks, 60% (SD 16) at 96 weeks, 52% (SD 18) at 144 weeks. The most common reason for treatment cessation was participant decision (11%, SD 6.6). Efficacy was higher with ‘Preferred’ than ‘Alternative’ regimens (as defined by 2013 United States antiretroviral guidelines): 75% vs. 65%, respectively, difference 10%; 95%CI 7.6 to 15.4; ppConclusionInitial antiretroviral treatments for HIV-1 to date appear to have suboptimal long-term efficacy, but are more effective when commenced at plasma viral loads背景 对人类免疫缺陷病毒1型（Human Immunodeficiency Virus Type 1, HIV-1）初始治疗效果的全面评估，可为研究设计与临床治疗指南的制定提供重要参考依据。方法 本研究针对截至2012年12月31日已发表的、纳入成年受试者、随访时长≥48周的初始抗反转录病毒治疗（antiretroviral therapy, ART）相关研究，开展了以研究组为单位的系统评价与荟萃分析。我们计算了经权重加权的意向治疗（intention-to-treat, ITT）疗效；提取了研究设计/入组标准、受试者特征与治疗方案特征等相关参数；随后采用带有向后逐步选择法的多变量随机效应线性回归模型，筛选与疗效相关的影响变量。结局指标 抗病毒疗效（血浆病毒载量低于检测下限）与治疗过早停药情况。结果 本研究共纳入114项研究，涵盖216个治疗组、40124名受试者；受试者平均CD4计数为248个/µL（标准差81），平均HIV-1血浆病毒载量对数值为4.9（标准差0.2）。所有治疗组的平均疗效为60%（标准差16），平均随访时长为82周（标准差38）。疗效随随访时间延长呈下降趋势：48周时为66%（标准差16），96周时为60%（标准差16），144周时为52%（标准差18）。治疗停药最常见的原因为受试者自行决定（占比11%，标准差6.6）。按照2013年美国抗反转录病毒治疗指南定义的「首选方案」，其疗效优于「备选方案」，分别为75%与65%，差值为10%；95%置信区间为7.6至15.4；结论 截至目前，HIV-1初始抗反转录病毒治疗的长期疗效似乎未达最优，但当在血浆病毒载量……