Definition of rapid virologic response with a highly sensitive real-time PCR-based HCV RNA assay in peginterferon alfa-2a plus ribavirin response-guided therapy

Abstract

Background & aims: Assessing hepatitis C virus (HCV)-RNA levels is integral to response-guided therapy. Rules for early discontinuation and determination of treatment duration were mainly established with HCV-RNA assays with a detection limit of 50IU/ml (COBAS Amplicor HCV [CA]). The currently used real-time PCR-based COBAS Ampliprep/COBAS-TaqMan HCV (CAP-CTM) test has a detection limit of approximately 10IU/ml. It is unknown whether shortening of treatment duration to 16/24 weeks in patients with rapid virological response at week 4 (RVR) and viral loads between 10 and 50IU/ml is possible.

Methods: We reanalysed stored serum from two large, multinational, randomized trials in which patients were treated with peginterferon alfa-2a/ribavirin (n=962). Results of CAP-CTM with truly undetectable HCV RNA and those <15IU/ml, which includes patients with residual viraemia (<15), were compared with the originally obtained results using the CA assay.

Results: RVR rates were comparable for CA (<50) and CAP-CTM (<15) with 32% and 32% for genotype (gt) 1 and 50% and 49% for gt2/3 patients, respectively. A significantly smaller number of samples really had truly undetectable HCV RNA by the CAP-CTM assay (24% for gt1, 37% for gt2/3). However, sustained virological response rates after shortened treatment (16/24weeks) were not significantly different in patients with a RVR <50, a RVR <15 and RVR undetectable (82%, 83%, 83% for 24weeks gt1 and 95%, 95%, 94% for 16weeks gt2/3).

Conclusions: Shortening the treatment duration to 16/24weeks can be performed on the basis of a RVR with HCV-RNA concentrations <15IU/ml by the CAP-CTM assay.