title: 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 RealTime HIV-1 assay.
  
  
  METHODS
  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 50copies/mL across all three platforms.
  
  
  RESULTS
  While good overall correlation was observed between the assays (r≥0.93), quantitative differences exceeded 0.5log(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 RealTime HIV-1 assay ranged from 0.04 to 0.15 (SD log(10)) and 1.34% to 8.37% (CV). Reproducibility at 50copies/mL for RealTime HIV-1, TaqMan, and Amplicor was 10.05, 11.04 and 5.07 (% CV), respectively.
  
  
  CONCLUSIONS
  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.
authors.affiliation: New South Wales State Reference Laboratory for HIV, St Vincent Hospital, Sydney, Australia. c.yan@amr.org.au
authors.forename: Celine S
authors.initials: CS
authors.lastname: Yan
authors.forename: Imelda
authors.initials: I
authors.lastname: Hanafi
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Kelleher
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Carr
authors.forename: Janaki
authors.initials: J
authors.lastname: Amin
authors.forename: Leon P
authors.initials: LP
authors.lastname: McNally
authors.forename: Philip H
authors.initials: PH
authors.lastname: Cunningham
mesh_terms: D015658:HIV Infections / Q000175:diagnosis* / Q000821:virology*; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D011933:Reagent Kits, Diagnostic; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D019562:Viral Load / Q000379:methods*
chemical_list: D011933:Reagent Kits, Diagnostic