DST-NRF Centre of Excellence in Epidemiological Modelling and Analysis (SACEMA), Stellenbosch University, Stellenbosch, South Africa.
Vitalant Research Institute, San Francisco, CA, United States of America.
PLoS One. 2019 Jul 26;14(7):e0220345. doi: 10.1371/journal.pone.0220345. eCollection 2019.
Two manufacturers, Maxim Biomedical and Sedia Biosciences Corporation, supply CDC-approved versions of the HIV-1 Limiting Antigen Avidity EIA (LAg) for detecting 'recent' HIV infection in cross-sectional incidence estimation. This study assesses and compares the performance of the two assays for incidence surveillance.
We ran both assays on a panel of 2,500 well-characterized HIV-1-infected specimens. We analysed concordance of assay results, assessed reproducibility using repeat testing and estimated mean durations of recent infection (MDRIs) and false-recent rates (FRRs) for a range of normalized optical density (ODn) thresholds, alone and in combination with viral load thresholds. We defined three hypothetical surveillance scenarios, similar to the Kenyan and South African epidemics, and a concentrated epidemic. These scenarios allowed us to evaluate the precision of incidence estimates obtained by means of various recent infection testing algorithms (RITAs) based on each of the two assays.
The Maxim assay produced lower ODn values than the Sedia assay on average, largely as a result of higher calibrator readings (mean OD of 0.749 vs. 0.643), with correlation of normalized readings lower (R2 = 0.908 vs. R2 = 0.938). Reproducibility on blinded control specimens was slightly better for Maxim. The MDRI of a Maxim-based algorithm at the 'standard' threshold (ODn ≤1.5 & VL >1,000) was 201 days (95% CI: 180,223) and for Sedia 171 (152,191). The difference Differences in MDRI were estimated at 32.7 (22.9,42.8) and 30.9 days (21.7,40.7) for the two algorithms, respectively. Commensurately, the Maxim algorithm had a higher FRR in treatment-naive subjects (1.7% vs. 1.1%). The two assays produced similar precision of incidence estimates in the three surveillance scenarios.
Differences between the assays can be primarily attributed to the calibrators supplied by the manufacturers. Performance for surveillance was extremely similar, although different thresholds were optimal (i.e. produced the lowest variance of incidence estimates) and at any given ODn threshold, different estimates of MDRI and FRR were obtained. The two assays cannot be treated as interchangeable: assay and algorithm-specific performance characteristic estimates must be used for survey planning and incidence estimation.
两家制造商，Maxim Biomedical 和 Sedia Biosciences Corporation，供应了经 CDC 批准的 HIV-1 限制抗原亲和力 EIA（LAg）版本，用于在横断面发病率估计中检测“近期”HIV 感染。本研究评估和比较了这两种检测方法在发病率监测中的性能。
我们在一个由 2500 个特征明确的 HIV-1 感染样本组成的面板上运行了这两种检测方法。我们分析了检测结果的一致性，使用重复检测评估了可重复性，并估计了一系列归一化光密度（ODn）阈值的近期感染平均持续时间（MDRI）和假近期率（FRR），以及单独和结合病毒载量阈值。我们定义了三个假设的监测情况，类似于肯尼亚和南非的流行情况，以及一个集中的流行情况。这些情况允许我们根据两种检测方法中的每一种评估各种近期感染检测算法（RITA）获得的发病率估计的精度。
Maxim 检测法的平均 ODn 值低于 Sedia 检测法，这主要是由于校准器读数较高（平均 OD 为 0.749 与 0.643），归一化读数的相关性较低（R2 = 0.908 与 R2 = 0.938）。在盲样对照标本上，Maxim 的重复性稍好一些。基于 Maxim 的算法在“标准”阈值（ODn ≤1.5 & VL >1,000）下的 MDRI 为 201 天（95%CI：180,223），而 Sedia 为 171（152,191）。两种算法的 MDRI 差异估计值分别为 32.7（22.9,42.8）和 30.9 天（21.7,40.7）。相应地，Maxim 算法在未经治疗的受试者中的 FRR 更高（1.7%比 1.1%）。两种检测方法在三种监测情况下产生了相似的发病率估计精度。
检测方法之间的差异主要归因于制造商提供的校准器。监测性能非常相似，尽管最佳的阈值不同（即产生发病率估计值方差最小），并且在任何给定的 ODn 阈值下，都可以获得不同的 MDRI 和 FRR 估计值。这两种检测方法不能互换使用：必须使用特定于检测方法和算法的性能特征估计值来进行调查规划和发病率估计。
