重新校准限制性抗原亲和力酶免疫测定法以确定不同HIV-1亚型近期感染的平均持续时间。
Recalibration of the limiting antigen avidity EIA to determine mean duration of recent infection in divergent HIV-1 subtypes.
作者信息
Duong Yen T, Kassanjee Reshma, Welte Alex, Morgan Meade, De Anindya, Dobbs Trudy, Rottinghaus Erin, Nkengasong John, Curlin Marcel E, Kittinunvorakoon Chonticha, Raengsakulrach Boonyos, Martin Michael, Choopanya Kachit, Vanichseni Suphak, Jiang Yan, Qiu Maofeng, Yu Haiying, Hao Yan, Shah Neha, Le Linh-Vi, Kim Andrea A, Nguyen Tuan Anh, Ampofo William, Parekh Bharat S
机构信息
International Laboratory Branch, Division of Global HIV/AIDS, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
The South African DST/NRF Centre of Excellence in Epidemiological Modelling and Analysis (SACEMA), University of Stellenbosch, Stellenbosch, South Africa; School of Computational and Applied Mathematics, University of the Witwatersrand, Johannesburg, South Africa.
出版信息
PLoS One. 2015 Feb 24;10(2):e0114947. doi: 10.1371/journal.pone.0114947. eCollection 2015.
BACKGROUND
Mean duration of recent infection (MDRI) and misclassification of long-term HIV-1 infections, as proportion false recent (PFR), are critical parameters for laboratory-based assays for estimating HIV-1 incidence. Recent review of the data by us and others indicated that MDRI of LAg-Avidity EIA estimated previously required recalibration. We present here results of recalibration efforts using >250 seroconversion panels and multiple statistical methods to ensure accuracy and consensus.
METHODS
A total of 2737 longitudinal specimens collected from 259 seroconverting individuals infected with diverse HIV-1 subtypes were tested with the LAg-Avidity EIA as previously described. Data were analyzed for determination of MDRI at ODn cutoffs of 1.0 to 2.0 using 7 statistical approaches and sub-analyzed by HIV-1 subtypes. In addition, 3740 specimens from individuals with infection >1 year, including 488 from patients with AIDS, were tested for PFR at varying cutoffs.
RESULTS
Using different statistical methods, MDRI values ranged from 88-94 days at cutoff ODn = 1.0 to 177-183 days at ODn = 2.0. The MDRI values were similar by different methods suggesting coherence of different approaches. Testing for misclassification among long-term infections indicated that overall PFRs were 0.6% to 2.5% at increasing cutoffs of 1.0 to 2.0, respectively. Balancing the need for a longer MDRI and smaller PFR (<2.0%) suggests that a cutoff ODn = 1.5, corresponding to an MDRI of 130 days should be used for cross-sectional application. The MDRI varied among subtypes from 109 days (subtype A&D) to 152 days (subtype C).
CONCLUSIONS
Based on the new data and revised analysis, we recommend an ODn cutoff = 1.5 to classify recent and long-term infections, corresponding to an MDRI of 130 days (118-142). Determination of revised parameters for estimation of HIV-1 incidence should facilitate application of the LAg-Avidity EIA for worldwide use.
背景
近期感染平均持续时间（MDRI）以及长期HIV-1感染的错误分类（以假近期比例，即PFR表示）是基于实验室检测估计HIV-1发病率的关键参数。我们和其他人最近对数据的审查表明，先前估计的LAg-Avidity酶免疫测定法的MDRI需要重新校准。我们在此展示了使用超过250个血清转化样本组和多种统计方法进行重新校准的结果，以确保准确性和一致性。
方法
如前所述，使用LAg-Avidity酶免疫测定法对从259名感染不同HIV-1亚型的血清转化个体收集的总共2737份纵向样本进行检测。使用7种统计方法在ODn临界值为1.0至2.0时分析数据以确定MDRI，并按HIV-1亚型进行亚分析。此外，对来自感染超过1年个体的3740份样本（包括488份来自艾滋病患者的样本）在不同临界值下检测PFR。
结果
使用不同的统计方法，在临界值ODn = 1.0时，MDRI值范围为88 - 94天，在ODn = 2.0时为177 - 183天。不同方法得到的MDRI值相似，表明不同方法具有一致性。对长期感染中的错误分类检测表明，在临界值从1.0增加到2.0时，总体PFR分别为0.6%至2.5%。综合考虑更长的MDRI和更小的PFR（<2.0%）的需求，表明对于横断面应用应使用临界值ODn = 1.5，对应MDRI为130天。MDRI在各亚型之间有所不同，从109天（A&D亚型）到152天（C亚型）。
结论
基于新数据和修订分析，我们建议使用ODn临界值 = 1.5来区分近期和长期感染，对应MDRI为130天（118 - 142天）。确定用于估计HIV-1发病率的修订参数应有助于LAg-Avidity酶免疫测定法在全球范围内的应用。
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