Factors associated with incorrect identification of recent HIV infection using the BED capture immunoassay

Abstract

The BED capture enzyme immunoassay (BED-CEIA) was developed for estimating HIV incidence from cross-sectional data. This assay misclassifies some individuals with nonrecent HIV infection as recently infected, leading to overestimation of HIV incidence. We analyzed factors associated with misclassification by the BED-CEIA. We analyzed samples from 383 men who were diagnosed with HIV infection less than 1 year after a negative HIV test (Multicenter AIDS Cohort Study). Samples were collected 2-8 years after HIV seroconversion, which was defined as the midpoint between the last negative and first positive HIV test. Samples were analyzed using the BED-CEIA with a cutoff of OD-n ≤ 0.8 for recent infection. Logistic regression was used to identify factors associated with misclassification. Ninety-one (15.1%) of 603 samples were misclassified. In multivariate models, misclassification was independently associated with highly active antiretroviral treatment (HAART) for >2 years, HIV RNA <400 copies/ml, and CD4 cell count <50 or <200 cells/mm(3); adjusted odds ratios (OR) and 95% confidence intervals (CI) were 4.72 (1.35-16.5), 3.96 (1.53-10.3), 6.85 (2.71-17.4), and 11.5 (3.64-36.0), respectively. Among 220 men with paired samples, misclassification 2-4 years after seroconversion was significantly associated with misclassification 6-8 years after seroconversion [adjusted OR: 25.8 (95% CI: 8.17-81.5), p<0.001] after adjusting for race, CD4 cell count, HIV viral load, and HAART use. Low HIV viral load, low CD4 cell count, and >2 years of HAART were significantly associated with misclassification using the BED-CEIA. Some men were persistently misclassified as recently infected up to 8 years after HIV seroconversion.

FIG. 1.

Comparison of paired BED capture enzyme immunoassay (CEIA) results within an individual 2–4 and 6–8 years after HIV seroconversion (Multicenter AIDS Cohort Study: 1987–2009). The x-axis shows the number of years between HIV seroconversion and sample collection. The y-axis shows the BED-CEIA result in normalized optical density (OD-n) units. Two samples from each individual were tested with the BED-CEIA: one collected 2–4 years after HIV seroconversion and one collected 6–8 years after HIV seroconversion; results from the two samples from each individual are connected with a gray line. (A) Data for men who had a CD4 cell count >50 cells/mm³ and an HIV viral load >400 copies/ml at 2–4 years who initiated HAART between the two time points and were receiving HAART 6–8 years after seroconversion. (B) Data for men who had a CD4 cell count >50 copies/mm³ 2–4 years after seroconversion and a CD4 cell count <50 copies/mm³ 6–8 years after seroconversion. (C) Data for men who had a CD4 cell count >50 cells/mm³ and an HIV viral load >400 copies/ml at both time points, and who were not receiving HAART. In each panel of the figure, a solid black line shows the regression line for all paired data; dashed black lines show the 95% confidence intervals for the regression line.