Lack of correlation between three commercial platforms for the evaluation of human immunodeficiency virus type 1 (HIV-1) viral load at the clinically critical lower limit of quantification

Abstract

Background Concordance in plasma HIV-1 viral load quantification at the lower limit of quantification (LLOQ) is crucial for current commercial assays. Objective To compare the performance of three commercial viral load assays and carry out a correlation study with the Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 test, the Roche Cobas Amplicor HIV-1 MONITOR test, and the Abbott RealTi me HIV-1 assay. Study design Assay agreement was analyzed using linear regression and Bland–Altman plots. Concordance near the clinically critical LLOQ was measured by Cohen's kappa statistics. Intra-assay precision was assessed, and assay reproducibility was measured at 50 copies/mL across all three platforms. Results While good overall correlation was observed between the assays ( r ≥ 0.93), quantitative differences exceeded 0.5 log 10 copies/mL among paired results in 3.7 to 8.3% of specimens. The degree of concordance between the assays near the LLOQ was unsatisfactory, with Cohen's kappa ranging from 0.14 to 0.38. The intra-assay precision of the Abbott RealTi me HIV-1 assay ranged from 0.04 to 0.15 (SD log 10) and 1.34% to 8.37% (CV). Reproducibility at 50 copies/mL for RealTi me HIV-1, TaqMan, and Amplicor was 10.05, 11.04 and 5.07 (% CV), respectively. Conclusion Although good correlation was observed between the assays across their linear range, their concordance at the clinically critical LLOQ was poor. The accurate quantification of low-level viremia remains elusive, and the lack of correlation of these assays presents a challenge to the interpretation of such results and in the clinical management of HIV-infected patients.