Recalibration of the limiting antigen avidity EIA to determine mean duration of recent infection in divergent HIV-1 subtypes.

Duong, Y.T.
Kassanjee, R.
Welte, A.
Ampofo, W.
Parekh, B.S.
Morgan, M.
De, A.
Dobbs, T.
Rottinghaus, E.
Nkengasong, J.
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Public Library of Science
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.
antigen, accuracy, acquired immune deficiency syndrome, analytical parameters, antigen binding, controlled study, disease duration, enzyme immunoassay, human, Human immunodeficiency virus 1, Human immunodeficiency virus 1 infection, limiting antigen vidity, major clinical study, mean duration of recent infection, proportion false recent, Review, seroconversion, statistical analysis, HIV infections, BIOLOGICAL assay, PARAMETER estimation, LONGITUDINAL method, DATA analysis
Duong, Y.T. et al. 2015. Recalibration of the limiting antigen avidity EIA to determine mean duration of recent infection in divergent HIV-1 subtypes. PLoS ONE 10(2): e0114947.