Multicenter Comparison Study of both Analytical and Clinical Performance across Four Roche Hepatitis C Virus RNA Assays Utilizing Different Platforms

Abstract

The efficacy of antiviral treatment for chronic hepatitis C virus (HCV) infection is determined by measuring HCV RNA at specific time points throughout therapy using highly sensitive and accurate HCV RNA assays. This study compared the performances of two recently developed real-time PCR HCV RNA assays, cobas HCV for use on the cobas 6800/8800 systems (cobas 6800/8800 HCV) and cobas HCV for use on the cobas 4800 system (cobas 4800 HCV), with those of two established assays, the Cobas AmpliPrep/Cobas TaqMan HCV quantitative test, version 2 (CAP/CTM v2) and the Cobas TaqMan HCV test, version 2 for use with the High Pure system (HPS/CTM v2). The limits of detection (LODs) and linearity at lower concentrations (5 to 1000 IU/ml) were assessed for cobas 6800/8800 HCV and cobas 4800 HCV using WHO standard traceable panels representing HCV genotypes (GT) 1 to 4. Pairwise assay comparisons were also performed using 245 clinical samples representing HCV GT 1 to GT 4. Results from cobas 6800/8800 HCV and cobas 4800 HCV were linear at low HCV RNA concentrations (<0.3 log10 IU/ml difference between expected and observed results) with LODs of 8.2 IU/ml and 11.7 IU/ml, respectively, for GT 1. The new assays showed excellent agreement with results from CAP/CTM v2 and HPS/CTM v2 in samples with quantifiable viral loads. The concordances using the 6 million IU/ml cutoff were high among all four assays (90 to 94%). In conclusion, the cobas 6800/8800 HCV and cobas 4800 HCV tests are sensitive and linear and correlate well with the established Roche assays used in clinical practice.

Evaluation of a quantitative RT-PCR assay for the detection of the emerging coronavirus SARS-CoV-2 using a high throughput system

“…The system has passed clinical evaluation for a variety of viral and bacterial targets [14][15][16][17] and is also used for blood safety testing, another diagnostic field in which large numbers of samples have to be cleared by PCRbased screening tests.…”

Analytical performance of four molecular platforms used for HIV-1, HBV and HCV viral load determinations

“…performance. To date, few published studies have compared the analytical performance of different next-generation assay platforms with higher levels of automation used for the measurement of VL, only four of which included c6800 [29,31,32,49], and only one with c6800 and Aptima results [49].…”

“…In the US, an HCV VL of 6,000,000 IU/mL is used as a cut-off point to identify treatment-naive noncirrhotic patients in whom a shorter (8 vs 12 weeks) course of ledipasvir/sofosbuvir is sufficient to treat genotype 1 infection [25,58]. Thus, under-quantification may lead to sub-optimally short duration of therapy and a lower likelihood of cure for some patients [31,59]. Similarly, for HIV-1, lower response rates and increased risk of development of drug resistance have been reported among subjects treated with rilpivirine who had baseline VL below 100,000 copies/mL [60] This study has several limitations.…”

“…VL measurements may be performed at different laboratories during long-term disease management, and variable assay performance may hamper the concordance and commutability of results and may lead to inappropriate treatment [26][27][28][29][30]. Commonly used VL tests include those manufactured by Roche (cobas 6800/8800; c6800) and cobas 4800 (c4800) systems [29,[31][32][33], Abbott (m2000 RealTime) [34,35], Hologic (Aptima, Panther) [36][37][38][39][40], Beckman (VERIS) [41][42][43][44][45][46][47][48] and others. Most of these assays rely on quantitative, real-time RT-PCR, while the Aptima assay uses transcription-mediated amplification (TMA), which may impart some differences in performance characteristics.…”

Generating timely molecular diagnostic test results: workflow comparison of the cobas® 6800/8800 to Panther

“…Multiple target, automated molecular testing instruments are manufactured by Roche (cobas 6800/8800 and cobas 4800 systems) [3][4][5][6], Abbott (m2000 RealTime and Alinity m) [7,8], Beckton-Dickinson (Viper, BD MAX) [9][10][11][12][13], Cepheid (Infinity80) [13,14] and Hologic (Aptima, Panther) [15][16][17][18][19]. Apart from Aptima assays on the Panther system, these systems rely on quantitative, real-time PCR to detect and/or quantitate various target analytes.…”