Human immunodeficiency virus (HIV) antibody avidity testing to identify recent infection in newly diagnosed HIV type 1 (HIV-1)-seropositive persons infected with diverse HIV-1 subtypes

Abstract

A guanidine-based antibody avidity assay for the identification of recently acquired human immunodeficiency virus type 1 (HIV-1) infection was evaluated. The kinetics of maturation of antibody avidity were determined prospectively in 23 persons undergoing acute seroconversion followed for up to 1,075 days. Avidity indices (AI) of <or=0.75 and <or=0.80 reproducibly identified seroconversion within the previous 125 (95% confidence interval [CI], 85 to 164) and 142 (95% CI, 101 to 183) days, respectively. To validate the assay, 432 serum samples from newly diagnosed patients were tested by both the avidity assay and the detuned assay. Results were highly concordant (kappa value for agreement, 0.85). The avidity assay was subsequently used to screen 134 consecutive newly diagnosed patients, including 55/134 (41%) infected with non-B subtypes (A, C, D, G, CRF01, CRF02, CRF06, CRF13, and CRF16). In this cohort, 25/79 (32%) persons with the B subtype and 7/55 (13%) with non-B subtypes showed an AI of <or=0.75, and there were 16/25 (64%) and 3/7 (43%) persons, respectively, with a documented history of acute seroconversion illness within the predicted seroconversion interval. An AI of <or=0.75 was also observed for four patients (three with the B subtype and one with a non-B subtype) who presented with AIDS-defining conditions. In multivariate analysis, an AI of <or=0.75 was associated with younger age, higher HIV-1 plasma RNA load, and being born in the United Kingdom or Ireland rather than in Africa but not with gender, ethnicity, risk group, HIV-1 subtype, or CD4 counts. In conclusion, HIV antibody avidity testing provides a reliable method for identifying recently acquired HIV-1 infection. Results are affected by advanced disease and should therefore be interpreted in the context of other clinical parameters.

FIG. 1.

Evolution of HIV-specific antibody avidity (expressed as avidity index) after HIV-1 seroconversion as determined for a patient infected with subtype B HIV-1 by either a guanidine-based assay or a urea-based assay and for a patient infected with F/complex non-B subtype mosaic HIV-1 by a guanidine-based assay.

FIG. 2.

Avidity index values observed with 72 serum samples collected from 23 HIV-1-infected persons at multiple points between day 0 and day 262 after HIV antibody seroconversion and tested by a guanidine-based HIV antibody avidity assay. The data points spanning the range of day 32 to day 153 (17 points) were analyzed by linear regression. The regression line (solid line) and 95% confidence prediction intervals (dotted lines) are shown.

FIG. 3.

Correlation between the HIV antibody avidity assay and the detuned assay. Samples obtained from 432 newly diagnosed HIV-1-infected patients were tested in by the guanidine-based HIV avidity assay and results reported as avidity indices, with values of ≤0.8 indicating seroconversion within the previous 142 days. Samples were also tested by the detuned assay and results reported as SOD, with values of ≤0.9 indicating seroconversion within the previous 150 days.