Recalibration of the Limiting Antigen Avidity EIA to Determine Mean Duration of Recent Infection in Divergent HIV-1 Subtypes

Abstract

BackgroundMean 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.MethodsA 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.ResultsUsing 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).ConclusionsBased 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.

Short Communication: Low False Recent Rate of Limiting-Antigen Avidity Assay Among Long-Term Infected Subjects from Guangxi, China

“…6 However, the results in this study were similar to the newly published study, 1.6%, 6 though the recently published study by the CDC did not stratify the FRR results by infecting subtype. A previous study from Vietnam showed a very low FFR for the BED Capture EIA (BED-CEIA), 7 and though the results of the BED-CEIA and LAg-Avidity assay are highly correlated, it is notable that the BED-EIA has a higher FRR than the LAg-Avidity.…”

“…4 Specifically, the test developers recommends a cutoff of a 1.5 normalized optical density (OD-n) and subsequent viral load confirmation (viral load >1,000 copies/ ml). 5,6 An additional recommendation is the generation of a local false-recent rate (FRR), which is the fraction of longterm infected (>2 years) who test positive for the testing algorithm. 5,7,8 In this report, we present LAg-Avidity assay results from individuals in Guangxi province of China who have been infected a median of 5.4 years (range 2.0 to 13.5 years), based on prior HIV antibody testing.…”

Estimating False-Recent Classification for the Limiting-Antigen Avidity EIA and BED-Capture Enzyme Immunoassay in Vietnam: Implications for HIV-1 Incidence Estimates

“…Although there was no statistically significant difference between the two assays, the point estimates for the LAg-Avidity EIA PFR were lower than the BED-CEIA, which complements previous demonstrations of improved performance characteristics of the LAg-Avidity EIA compared with the BED-CEIA. 16,25 The better performance of LAg-Avidity EIA is likely attributed to the design of the assay to measure HIV antibody avidity compared to the BED-CEIA, which is a capture EIA that measures the proportion of anti-HIV IgG to total IgG.…”

Short Communication: Heightened HIV Antibody Responses in Postpartum Women as Exemplified by Recent Infection Assays: Implications for Incidence Estimates

“…These were 33%, 32%, and 52% lower than published estimates of 287 (248–328), 152 (128–178), and 298 (262–338) days for respective assays of clade C samples. 1,3,6 Other analyses (data not shown) showed that MDRIs do not differ significantly with the estimation method.…”

“…1 A case is defined as recent when the optical density, or avidity index, measured using a chosen biomarker, is less than some preset cutoff ( C ). In southern Africa, MDRI values were first estimated for the multi-subtype peptide representing subtypes B, E and D (BED)-capture enzyme immunoassay using samples collected in Harare from 1997 to 2000 during the Zimbabwe Vitamin A for Mothers and Babies (ZVITAMBO) trial.…”