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

BackgroundEarly on-treatment virological response is one of the most important predictors 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. 48weeks) is based on HCV RNA results at weeks 4 and 12 of PI therapy when HCV RNA must be undetectable' to allow shorter therapy. AimTo analyse the reliability of HCV RNA measurements at key decision time points (weeks 4 and 12) and the predictive value of concordant or discordant assay results for SVR. MethodsWeeks 4 and 12 samples of patients receiving telaprevir-containing triple therapy were initially tested with the AmpliPrep/COBAS-TaqMan_HCV-Test-v1.0 (limit of detection; LOD=15IU/mL) and retested with the AmpliPrep/COBAS-TaqMan_HCV-Test-v2.0 (LOD=15IU/mL) and the High_Pure/COBAS-TaqMan_HCV-Test-v2.0 (LOD=20IU/mL). ResultsConcordance among the three test results in classifying samples as HCV RNA undetectable' or detectable' was only 55% at week 4, but 85% at week 12. Retesting of undetectable' week 4 samples with the respective other assays revealed positive HCV RNA results in 32-50%. In 30%, HCV RNA was undetectable' by all three tests at week 4 and all of these patients achieved SVR. In contrast, treatment failure occurred in 62% of patients with at least one detectable' result, including cases with one or two other undetectable' tests at week 4. ConclusionsA single undetectable' HCV RNA result at week 4 is not always associated with achieving SVR. Repeated testing in difficult-to-treat patients may identify those at risk for treatment failure.