Detection of low HCV viremia by repeated HCV RNA testing predicts treatment failure to triple therapy with telaprevir

Backgrounds/Aims: Early on-treatment virological response is one of the most important predictor for sustained virological response (SVR) to treatment of chronic hepatitis C virus (HCV) genotype 1 infection with triple therapy including HCV protease inhibitors (PI). Treatment duration (24 vs. 48 weeks) is based on HCV RNA results at weeks 4 and 12 of PI therapy when HCV RNA must be “undetectable” to allow shorter therapy. We aimed to analyze the reliability of HCV RNA measurements at these decision time points as well as the predictive value of concordant or discordant assay results for SVR.

Methods: Week 4 and 12 samples of patients receiving telaprevir-containing triple therapy were initially tested with the COBAS_AmpliPrep/COBAS® TaqMan HCV-Test-v1.0 and re-tested with the COBAS_AmpliPrep/COBAS® TaqMan HCV-Test-v2.0 and the COBAS®_TaqMan® HCV-Test-v2.0.

Results: Concordance between the three testings in classifying samples to be HCV RNA “undetectable”, “detectable/not quantifiable” or “quantifiable” was only 46% at week 4 but 85% at week 12. Re-testing of “undetectable” week 4 samples with the respective other assays revealed positive HCV RNA results in 35 – 50%. In 31% HCV RNA was “undetectable” by all three testings at week 4 and all of these patients achieved a SVR. In contrast, treatment failure occurred in 62% of patients with at least one “detectable” result including cases with one or two “undetectable” tests at week 4.

Conclusions: A single “undetectable” HCV RNA result at week 4 is not always associated with achieving SVR. Thus repeated testing may identify patients at risk for treatment failure.