Division of Global HIV & TB, Centers for Disease Control and Prevention, Atlanta, GA, United States of America.
Global Health Fellowship Program, Public Health Institute/Centers for Disease Control, Atlanta, GA, United States of America.
PLoS One. 2024 Oct 25;19(10):e0311829. doi: 10.1371/journal.pone.0311829. eCollection 2024.
We developed the HIV Triplex multiplex bead assay to identify and serotype HIV infection with high sensitivity and specificity; and distinguish recent from long-term HIV-1 infections. It can facilitate accurate incidence estimation, while reducing the number of tests and blood collected, which is highly desirable for use in future studies and surveys. Using previously collected, treatment-naive longitudinal seroconversion HIV-1 positive panels and specimens from individuals infected for >12 months, we determined the assay's mean duration of recent infection (MDRI) and false-recency rate (FRR) respectively, at various mean fluorescent intensity (MFI) cutoffs.
We tested seroconversion specimens (N = 814) from 142 individuals infected with HIV-1 subtypes B, C, or AE, and 1341 cross-sectional specimens from individuals infected >12 months. The MFI cutoffs of 1000 to 2000 were evaluated for recency classification, including an MFI of 1250 corresponding to the limiting antigen avidity enzyme immunoassay (LAg-EIA) cutoff of 1.5 normalized optical density for MDRI and FRR. We used four statistical methods: Methods 1 and 2 used the empirically balanced observation time approach. Method 2 MFI values were raised to power = 1.33, based on a repeated measures model to linearize the relationship between MFI and time points, whereas Method 1 was not linearized. Methods 3 and 4 employed quadratic and linear interpolations for each seroconversion panel. FRR was calculated by dividing the number of specimens misclassified as recent by the total number of specimens tested.
MDRI values ranged from 135-146 days at MFI = 1000 to 229-279 days at MFI = 2000 by the 4 methods. FRR varied from 0.15%-1.27% with increasing MFI cutoff. At MFI = 1250, the average MDRI of 4 methods was 169 days and ranged from 159-183 with overlapping 95% CIs and FRR = 0.52%.
The HIV Triplex assay demonstrates a longer dynamic range compared to current HIV recency assays with a low FRR for cutoffs examined. With a longer dynamic range and low FRR, the MDRI for recent infection can be extended as appropriate to detect more recent infections, increasing the value of incidence assays benefiting public health surveillance and future surveys.
我们开发了 HIV 三联多重珠粒检测法，以高灵敏度和特异性识别和定型 HIV 感染，并区分近期和长期的 HIV-1 感染。它可以方便准确地估计发病率，同时减少测试次数和采集的血液量，这对于未来的研究和调查非常理想。我们使用先前收集的、未经治疗的纵向血清转化 HIV-1 阳性面板和感染超过 12 个月的个体的标本，分别确定了该检测方法在不同平均荧光强度 (MFI) 截止值下的近期感染平均持续时间 (MDRI) 和假近期率 (FRR)。
我们测试了 142 名感染 HIV-1 亚型 B、C 或 AE 的个体的血清转化标本（N=814）和 1341 名感染超过 12 个月的个体的横断面标本。评估了 1000 至 2000 的 MFI 截止值用于近期分类，包括对应于 1.5 归一化光密度的限制抗原亲和力酶免疫测定 (LAg-EIA) 截止值 1250 的 MFI，用于 MDRI 和 FRR。我们使用了四种统计方法：方法 1 和 2 使用经验平衡观察时间方法。方法 2 将 MFI 值提高到幂 = 1.33，基于重复测量模型将 MFI 与时间点之间的关系线性化，而方法 1 没有线性化。方法 3 和 4 为每个血清转化面板使用二次和线性插值。FRR 通过将最近分类错误的标本数量除以测试的标本总数来计算。
四种方法的 MDRI 值范围为 MFI=1000 时的 135-146 天到 MFI=2000 时的 229-279 天。FRR 随 MFI 截止值的增加而变化，范围为 0.15%-1.27%。在 MFI=1250 时，四种方法的平均 MDRI 为 169 天，95%CI 重叠范围为 159-183，FRR=0.52%。
与当前的 HIV 近期检测方法相比，HIV 三联检测法具有更长的动态范围和更低的 FRR，适用于检测更近期的感染，增加了发病率检测的价值，有利于公共卫生监测和未来的调查。
