Infection Staging and Incidence Surveillance Applications of High Dynamic Range Diagnostic Immuno-Assay Platforms.
Infection Staging and Incidence Surveillance Applications of High Dynamic Range Diagnostic Immuno-Assay Platforms.
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DOI：
10.1097/qai.0000000000001537
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发表时间：
2017-12-15
期刊：
影响因子：
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通讯作者：
Murphy G
中科院分区：
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作者：
Grebe E;Welte A;Hall J;Keating SM;Facente SN;Marson K;Martin JN;Little SJ;Price MA;Kallas EG;Busch MP;Pilcher CD;Murphy G
自定义HIV分期检测试剂盒（包括Sedia™ HIV-1限制性抗原亲合力EIA（LAg）和Ortho VITROS® anti-HIV-1+2和Abbott ARCHITECT HIV Ag/Ab Combo检测试剂盒的亲合力改良）用于识别临床环境中的“近期”感染和横断面HIV发病率估计。然而，荧光平台的高动态范围允许在信号强度上区分近期和长期感染，并且这提高了使用未修饰的诊断测定用于感染定时和监测应用的前景。我们使用三种检测试剂盒和未修饰的ARCHITECT检测了一组2，500份具有可估计的HIV感染持续时间的充分表征的标本。回归模型用于估计近期感染的平均持续时间（MDRI）、特定背景的假近期率（FRR）以及诊断信号强度与LAg测量值之间的相关性。建立了假设的流行病学情景，以评估监测应用中的效用。在一定范围的MDRI（反映了近期辨别阈值）内，稀释的基于ARCHITECT的RITA产生的FRR低于VITROS平台（在MDRI ≥ 200天时，FRR分别为0.5%和1.5%），未修改的诊断ARCHITECT产生的发生率估计值与LAg具有可比精度（在MDRI ≥ 200天时，RSE分别为17.5%和15%）。ARCHITECT S/CO测量值与LAg ODn测量值高度相关（r = 0.80），低于200的值强烈预测LAg近发性和感染持续时间小于1年。来自未改良ARCHITECT的低定量测量结果表明需要额外的近因检测，并且其在临床分期和发病率监测应用中是可行的。
Custom HIV staging assays, including the Sedia™ HIV-1 Limiting Antigen Avidity EIA (LAg) and avidity modifications of the Ortho VITROS® anti-HIV-1+2 and Abbott ARCHITECT HIV Ag/Ab Combo assays, are used to identify ‘recent’ infections in clinical settings and for cross-sectional HIV incidence estimation. However, the high dynamic range of chemiluminescent platforms allows differentiating recent and longstanding infection on signal intensity, and this raises the prospect of using unmodified diagnostic assays for infection timing and surveillance applications. We tested a panel of 2,500 well-characterised specimens with estimable duration of HIV infection with the three assays and the unmodified ARCHITECT. Regression models were used to estimate mean durations of recent infection (MDRI), context-specific false-recent rates (FRR) and correlation between diagnostic signal intensity and LAg measurements. Hypothetical epidemiological scenarios were constructed to evaluate utility in surveillance applications. Over a range of MDRIs (reflecting recency discrimination thresholds), a diluted ARCHITECT-based RITA produced lower FRRs than the VITROS platform (FRR ≈ 0.5% and 1.5% respectively at MDRI ≈ 200 days) and the unmodified diagnostic ARCHITECT produces incidence estimates with comparable precision to LAg (RSE ≈ 17.5% and 15% respectively at MDRI ≈ 200 days). ARCHITECT S/CO measurements were highly correlated with LAg ODn measurements (r = 0.80) and values below 200 are strongly predictive of LAg recency and duration of infection less than one year. Low quantitative measurements from the unmodified ARCHITECT obviate the need for additional recency testing and its use is feasible in clinical staging and incidence surveillance applications.