O113: How different are quantitative HCV RNA assays?

Abstract

Response guided therapy has been developed for treatment of chronic hepatitis C aiming to optimize treatment duration in patients with virologic response and to stop antiviral therapy as early as possible in those with virologic non-response. The key parameter to guide treatment duration is HCV RNA concentration. Patients with undetectable HCV RNA early during treatment (week 4 of PEG-Interferon/Ribavirin dual combination and week 4 of Boceprevir/Telaprevir triple therapy, respectively) are eligible for shortening treatment duration to 24-28 weeks, instead of 48 weeks. While such a rapid virologic response (RVR) was observed in only approximately 15% of genotype one infected patients during dual combination therapy, 40-60% of patients on Boceprevir/Telaprevir triple therapy can achieve this goal. According to the approval studies and FDA/EMA recommendations completely undetectable HCV RNA levels at week 4 of triple therapy are required for eligibility of shortened treatment. However, while in phase 2-3 studies always one specific HCV RNA assay based on manual sample preparation was utilized (High Pure System/Cobas TaqMan v2.0 assay, Roche Diagnostics) in the real world other, highly automated HCV RNA assays are also available and widely used. Comparative studies between the Roche Cobas Taq- Man assays and the Abbott RealTime HCV test revealed significant differences of HCV RNA undetectability rates between different HCV RNA assays which led to a 26% smaller rate of patients eligible for short treatment by the Abbott assay without significant differences in SVR rates. Comparative data for other commercial available HCV RNA assays (Siemens kPCR, Qiagen Artus system etc.) are not available yet, but differences are to be expected. Overall, it becomes clear that separate cut-offs for different HCV RNA assays have to be established to permit a maximum of patients to benefit from short treatment. Next generation protease-inhibitor based triple therapies with Simeprevir and Faldaprevir also rely on response guided therapy approaches based on HCV RNA kinetics. Only with the approval of fixed treatment schedules (i.e., Sofosbuvir- based conventional triple therapy and interferonfree treatment options) the importance of HCV RNA measurement to guide duration of antiviral therapy will decline in the future.