Evolutionary dynamics of the E1-E2 viral populations during combination therapy in non-responder patients chronically infected with hepatitis C virus subtype 1b

Half of the patients chronically infected with hepatitis C virus (HCV) genotype 1 fail to respond to pegylated interferon alpha (PEG-IFN) and ribavirin (RBV) therapy. This study assesses the effects of treatment on the evolution of the E1-E2 viral region in non-responder patients infected with HCV-1b. Twenty-three HCV-1b chronically infected patients were studied retrospectively, including 19 non-responders to PEG-IFN/RBV therapy (11 null-responders and 8 relapsers) in the study group, and 4 untreated patients in the control group. Genetic and phylogenetic analyses of the E1-E2 viral populations were performed at baseline and at the time of treatment failure to assess changes in genetic variability and evolutionary dynamics during treatment. Baseline virological characteristics were similar in null-responders, relapsers and controls. E1-E2 genetic variability decreased during treatment in non-responders, with a more pronounced decline in relapsers than in null-responders. A specific evolutionary pattern was not observed in null-responders, while a complete substitution of viral variants found at baseline characterised relapser patients. No specific E1-E2 amino acid substitution involved in treatment failure could be identified. In conclusion, although diverse evolutionary patterns with no apparent common adaptive changes were observed during therapy, treatment failure was characterised by a decline in genetic diversity.

► Effects of PEG-IFN/RBV treatment on the HCV-1b E1-E2 region evolution in non-responder patients. ► Treatment failure is characterized by a decline in E1-E2 genetic diversity. ► This decline is more pronounced in relapsers than in null-responder patients. ► A complete substitution of viral variants characterises relapser patients. ► No specific E1-E2 amino acid substitution is involved in treatment failure.