Hepatitis C RNA assay differences in results: Potential implications for shortened therapy and determination of Sustained Virologic Response

Abstract

Approval of Ledipasvir/Sofosbuvir for the treatment of chronic hepatitis C (HCV) includes the truncation of therapy from 12 to 8 weeks in treatment naïve, non-cirrhotic patients with baseline HCV RNA levels <6 million IU/mL (6.8 log10 IU/mL). The aim of this study was to evaluate this clinical cutoff with a different widely used commercially available HCV RNA test. Results from samples tested prospectively with Roche High Pure TaqMan HCV 2.0 test (HPS) were compared to those tested retrospectively with the Abbott RealTime HCV RNA test (ART). Using 6 million IU/mL as the cut-off, pre-treatment results were concordant in 70.4% of cases. When results with the same test measured at screening and baseline, clinical decisions could be impacted in 14.4% and 6.2% of cases for HPS and ART respectively. Using only HCV RNA cutoff of 6 million IU/mL, 29.55% of subjects would receive a different and potentially incorrect treatment duration based solely on HCV RNA test method used. A further 6-14% of subjects would have treatment decision change based on the day the sample was taken.

Trial registration: ClinicalTrials.gov NCT01716585.

Figure 1. Breakdown of samples tested with both Roche High Pure HCV RNA 2.0 and Abbott RealTime HCV RNA tests by timepoint.

Figure 2. Least-Squares regression between Abbott RealTime HCV vs Roche HPS/TaqMan 2.0 for all data points within the dynamic range of both assays.

Clinically significant discordant results are found in red box.

Figure 3. Bland Altman Bias Plot Abbott RealTime HCV vs Roche HPS/TaqMan 2.0 for samples with viral load 25 IU/mL or Greater (n = 1011).

The mean difference between the two assays was −0.50 (95% Confidence Interval: −0.53 and −0.48; p < 0.0001) log₁₀ IU/mL HCV RNA.

Figure 4. ROC analysys of all available pre-treatment viral load measurements with both Roche HPS/TaqMan 2.0 HCV and Abbott RealTime HCV assays.

For this analysis Roche HPS/TaqMan 2.0 HCV was considered gold standard.

Figure 5. Samples with Roche HPS/TaqMan 2.0 HCV results falling within log intervals of the assays dynamic range were adjusted based on the calculated negative bias observed with the Abbott RealTime HCV test.

The linear regression of mean expected results compared to the mean expected results adjusted for bias.

Figure 6

(a) Percent detected by Abbott RealTime HCV (ART) and Roche HPS/TaqMan 2.0 HCV using 25 IU/mL as cut-off. DBD = Double Blind Day; OLW = Open Label Week; PSTW = Post Treatment Week. (b) Percent detected by Abbott RealTime HCV (ART) and Roche HPS/TaqMan 2.0 HCV using 100 IU/mL as cut-off. DBD = Double Blind Day; OLW = Open Label Week; PSTW = Post Treatment Week.