TY - JOUR
T1 - Recalibration of the limiting antigen avidity EIA to determine mean duration of recent infection in divergent HIV-1 subtypes
AU - Duong, Yen T.
AU - Kassanjee, Reshma
AU - Welte, Alex
AU - Morgan, Meade
AU - De, Anindya
AU - Dobbs, Trudy
AU - Rottinghaus, Erin
AU - Nkengasong, John
AU - Curlin, Marcel E.
AU - Kittinunvorakoon, Chonticha
AU - Raengsakulrach, Boonyos
AU - Martin, Michael
AU - Choopanya, Kachit
AU - Vanichseni, Suphak
AU - Jiang, Yan
AU - Qiu, Maofeng
AU - Yu, Haiying
AU - Hao, Yan
AU - Shah, Neha
AU - Le, Linh Vi
AU - Kim, Andrea A.
AU - Nguyen, Tuan Anh
AU - Ampofo, William
AU - Parekh, Bharat S.
N1 - Funding Information:
This research has been supported by the President’s Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention (CDC). The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the CDC/Agency for Toxic Substances and Disease Registry. AW and RK are grateful for support from the Bill and Melinda Gates Foundation through (and to their colleagues at) the Consortium for the Evaluation and Performance of HIV Incidence Assays, and the HIV Modeling Consortium.
Funding Information:
Statistical methods used to determine MDRIs have varied since the first description of the detuned assay in 1998 []. Since then multiple approaches have been used, partly due to lack of consensus among statisticians about the best methods [,,,,,,]. Under the auspices of WHO Incidence Working Group, a statistical workshop was organized in 2011 to develop a consensus and promote a preferred method(s). Although there was some broad agreement and a better understanding of various approaches used, differences in the approaches remain, and no detailed benchmarking has been carried out. Recently, a benchmarking project has been launched under the auspices of the HIV Modeling Consortium (funded by the Bill and Melinda Gates Foundation) with a focus on identifying strengths and limitations of a diverse range of methods. Our analyses show that when used appropriately with a robust dataset, several of these methods yield comparable estimates of MDRIs.
Publisher Copyright:
© 2015, Public Library of Science. All rights reserved.
PY - 2015/2/24
Y1 - 2015/2/24
N2 - 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 formisclassification among long-terminfections 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.
AB - 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 formisclassification among long-terminfections 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.
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U2 - 10.1371/journal.pone.0114947
DO - 10.1371/journal.pone.0114947
M3 - Review article
C2 - 25710171
AN - SCOPUS:84923375319
SN - 1932-6203
VL - 10
JO - PLoS One
JF - PLoS One
IS - 2
M1 - e0114947
ER -