Systematic Review of the Performance of HIV Viral Load Technologies on Plasma Samples

BackgroundViral load (VL) monitoring is the standard of care in developing country settings for detecting HIV treatment failure. Since 2010 the World Health Organization has recommended a phase-in approach to VL monitoring in resource-limited settings. We conducted a systematic review of the accuracy and precision of HIV VL technologies for treatment monitoring.Methods and FindingsA search of Medline and Embase was conducted for studies evaluating the accuracy or reproducibility of commercially available HIV VL assays. 37 studies were included for review including evaluations of the Amplicor Monitor HIV-1 v1.5 (n = 25), Cobas TaqMan v2.0 (n = 11), Abbott RealTime HIV-1 (n = 23), Versant HIV-1 RNA bDNA 3.0 (n = 15), Versant HIV-1 RNA kPCR 1.0 (n = 2), ExaVir Load v3 (n = 2), and NucliSens EasyQ v2.0 (n = 1). All currently available HIV VL assays are of sufficient sensitivity to detect plasma virus levels at a lower detection limit of 1,000 copies/mL. Bias data comparing the Abbott RealTime HIV-1, TaqMan v2.0 to the Amplicor Monitor v1.5 showed a tendency of the Abbott RealTime HIV-1 to under-estimate results while the TaqMan v2.0 overestimated VL counts. Compared to the Amplicor Monitor v1.5, 2–26% and 9–70% of results from the Versant bDNA 3.0 and Abbott RealTime HIV-1 differed by greater than 0.5log10. The average intra and inter-assay variation of the Abbott RealTime HIV-1 were 2.95% (range 2.0–5.1%) and 5.44% (range 1.17–30.00%) across the range of VL counts (2log10–7log10).ConclusionsThis review found that all currently available HIV VL assays are of sufficient sensitivity to detect plasma VL of 1,000 copies/mL as a threshold to initiate investigations of treatment adherence or possible treatment failure. Sources of variability between VL assays include differences in technology platform, plasma input volume, and ability to detect HIV-1 subtypes. Monitoring of individual patients should be performed on the same technology platform to ensure appropriate interpretation of changes in VL.Prospero registration # CD42013003603.

背景：病毒载量（viral load, VL）监测是发展中国家检测人类免疫缺陷病毒（HIV）治疗失败的临床标准诊疗方案。自2010年起，世界卫生组织（World Health Organization, WHO）便推荐在资源有限地区采用分阶段实施策略推行病毒载量监测。本研究针对用于HIV治疗监测的病毒载量检测技术的准确性与精密度开展了系统综述。
研究方法与结果：通过检索Medline与Embase数据库，筛选评估市售HIV病毒载量检测试剂盒准确性或可重复性的相关研究。最终纳入37项相关研究，涵盖对以下试剂的评估：Amplicor Monitor HIV-1 v1.5（n=25）、Cobas TaqMan v2.0（n=11）、Abbott RealTime HIV-1（n=23）、Versant HIV-1 RNA bDNA 3.0（n=15）、Versant HIV-1 RNA kPCR 1.0（n=2）、ExaVir Load v3（n=2）以及NucliSens EasyQ v2.0（n=1）。
所有当前可用的HIV病毒载量检测试剂盒均具备足够灵敏度，可在最低检测限1000拷贝/mL的条件下检出血浆病毒水平。对比Abbott RealTime HIV-1、TaqMan v2.0与Amplicor Monitor v1.5的偏倚数据显示，Abbott RealTime HIV-1存在低估检测结果的趋势，而TaqMan v2.0则倾向于高估病毒载量数值。以Amplicor Monitor v1.5为参照基准，Versant bDNA 3.0与Abbott RealTime HIV-1的检测结果中，分别有2%~26%、9%~70%的结果偏差超过0.5log10。在病毒载量范围2log10~7log10内，Abbott RealTime HIV-1的平均批内变异系数与批间变异系数分别为2.95%（区间2.0%~5.1%）与5.44%（区间1.17%~30.00%）。
结论：本综述表明，当前所有可用的HIV病毒载量检测试剂盒均具备足够灵敏度，可检出1000拷贝/mL的血浆病毒载量，以此作为阈值启动治疗依从性调查或排查潜在治疗失败的依据。不同病毒载量检测试剂盒间的变异来源包括技术平台差异、血浆样本输入体积差异以及对HIV-1亚型的检测能力差异。为确保对病毒载量变化的准确解读，对单个患者的监测应使用同一技术平台的检测试剂。
Prospero注册编号：CD42013003603。