title: Comparison of Three Different FDA-Approved Plasma HIV-1 RNA Assay Platforms Confirms the Virologic Failure Endpoint of 200 Copies per Milliliter Despite Improved Assay Sensitivity.
abstract: Discrepancies between HIV-1 RNA results assayed by different FDA-approved platforms have been reported. Plasma samples collected from 332 randomly selected clinical trial participants during the second year of antiretroviral treatment were assayed with three FDA-approved platforms: UltraSensitive Roche Amplicor Monitor, v1.5 (Monitor), the Abbott RealTime HIV-1 test on the m2000 system (Abbott), and the Roche TaqMan HIV-1 test, v2.0 (TaqMan). Samples from 61 additional participants with confirmed HIV-1 RNA levels of >50 copies/ml during trial follow-up were also included. Endpoints were HIV-1 RNA quantification of ≤50 copies/ml versus >50 copies/ml at an individual-sample level (primary) and determination of confirmed virologic failure (VF) from longitudinal samples. A total of 389 participants had results obtained from all assays on at least one sample (median = 6). Proportions of results of >50 copies/ml were 19% (Monitor), 22% (TaqMan), and 25% (Abbott). Despite indication of strong agreement (Cohen's kappa, 0.76 to 0.82), Abbott was more likely to detect HIV-1 RNA levels of >50 copies/ml than Monitor (matched-pair odds ratio [mOR] = 4.2; modified Obuchowski P < 0.001) and TaqMan (mOR = 2.1; P < 0.001); TaqMan was more likely than Monitor (mOR = 2.6; P < 0.001). Despite strong agreement in classifying VF across assay comparisons (kappa, 0.75 to 0.92), at a 50-copies/ml threshold, differences in the probability of VF classification (in the same direction as primary) were apparent (all McNemar's P < 0.007). At a 200-copies/ml VF threshold, no differences between assays were apparent (all P > 0.13). Despite strong agreement among assays, significant differences were observed with respect to detecting HIV-1 RNA levels of >50 copies/ml and identifying VF at the 50-copies/ml threshold. This has important implications for the definition of VF in clinical trials and clinical practice.
authors.affiliation: Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA lalama@sdac.harvard.edu.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Lalama
authors.affiliation: Rush University Medical Center, Chicago, Illinois, USA.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Jennings
authors.affiliation: Birmingham Veterans Affairs Medical Center and University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, USA.
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Johnson
authors.affiliation: University of Washington, Seattle, Washington, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Coombs
authors.affiliation: Henry Ford Hospital, Detroit, Michigan, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: McKinnon
authors.affiliation: Rush University Medical Center, Chicago, Illinois, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Bremer
authors.affiliation: Roche Molecular Systems, Pleasanton, California, USA.
authors.forename: Bryan R
authors.initials: BR
authors.lastname: Cobb
authors.affiliation: Abbott Molecular, Des Plaines, Illinois, USA.
authors.forename: Gavin A
authors.initials: GA
authors.lastname: Cloherty
authors.affiliation: University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Mellors
authors.affiliation: Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Ribaudo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000821:virology*; D012367:RNA, Viral / Q000097:blood*; D012680:Sensitivity and Specificity; D017211:Treatment Failure; D019562:Viral Load / Q000379:methods*; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents; D012367:RNA, Viral