Analysis of Viral Diversity in Relation to the Recency of HIV-1C Infection in Botswana.
Analysis of Viral Diversity in Relation to the Recency of HIV-1C Infection in Botswana.
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DOI：
10.1371/journal.pone.0160649
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
de Oliveira T
中科院分区：
文献类型：
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作者：
Moyo S;Vandormael A;Wilkinson E;Engelbrecht S;Gaseitsiwe S;Kotokwe KP;Musonda R;Tanser F;Essex M;Novitsky V;de Oliveira T
横断面，生物标志物的方法来确定艾滋病毒感染的新近性提出了一个有前途的和成本效益的替代重复测试的未感染的个人。我们评估了一种基于病毒的检测方法，该方法使用成对距离（PwD）来确定HIV感染的新近性，并将其性能与两种血清学发病率检测方法BED和LAg进行了比较。此外，我们还评估了BED + PwD或LAg + PwD联合筛查是否可以通过降低假近期结果的可能性来提高预测准确性。这些数据来自854个时间点和42名参与者，他们参加了博茨瓦纳的一项主要HIV-1C感染研究。治疗开始后或有多重感染证据的时间点从最终分析中排除。从使用单基因组扩增和测序产生的准种计算PwD。我们使用受试者操作特征（ROC）方法评估了PwD在血清转换后<130、<180和<360天内正确分类HIV感染近度的能力。在二次PwD筛查后，我们量化了BED和LAg检测的相对假近率（rFRR）的降低，同时保持75%、80%、85%或90%的灵敏度。最终的分析样本包括来自40名参与者的758个时间点。与推荐的LAg和BED阈值相比，PwD检测在130和180天临界值的感染新近度分类方面更准确。较高的AUC统计量证实了PwD测定法在三个临界值方面的上级预测性能。当用于组合筛选时，PwD检测使LAg检测的rFRR降低了52%，BED检测降低了57.8%，同时分别在130和180天的临界值下保持90%的灵敏度。PwD可以准确地确定HIV感染的新近度。二次PwD筛查减少了错误分类，并提高了基于血清学的检测的准确性。
Cross-sectional, biomarker methods to determine HIV infection recency present a promising and cost-effective alternative to the repeated testing of uninfected individuals. We evaluate a viral-based assay that uses a measure of pairwise distances (PwD) to identify HIV infection recency, and compare its performance with two serologic incidence assays, BED and LAg. In addition, we assess whether combination BED plus PwD or LAg plus PwD screening can improve predictive accuracy by reducing the likelihood of a false-recent result. The data comes from 854 time-points and 42 participants enrolled in a primary HIV-1C infection study in Botswana. Time points after treatment initiation or with evidence of multiplicity of infection were excluded from the final analysis. PwD was calculated from quasispecies generated using single genome amplification and sequencing. We evaluated the ability of PwD to correctly classify HIV infection recency within <130, <180 and <360 days post-seroconversion using Receiver Operator Characteristics (ROC) methods. Following a secondary PwD screening, we quantified the reduction in the relative false-recency rate (rFRR) of the BED and LAg assays while maintaining a sensitivity of either 75, 80, 85 or 90%. The final analytic sample consisted of 758 time-points from 40 participants. The PwD assay was more accurate in classifying infection recency for the 130 and 180-day cut-offs when compared with the recommended LAg and BED thresholds. A higher AUC statistic confirmed the superior predictive performance of the PwD assay for the three cut-offs. When used for combination screening, the PwD assay reduced the rFRR of the LAg assay by 52% and the BED assay by 57.8% while maintaining a 90% sensitivity for the 130 and 180-day cut-offs respectively. PwD can accurately determine HIV infection recency. A secondary PwD screening reduces misclassification and increases the accuracy of serologic-based assays.