16th International HIV Drug Resistance Workshop 12-16 June 2007, Barbados

QUASISPECIES ANALYSIS IN NON-STRUCTURAL 5A (NS5A) REGION OF HEPATITIS C VIRUS (HCV) GENOTYPE 1B IN INTERFERON (IFN) OR COMBINED INTERFERON-RIBAVIRIN (IFN-R) THERAPY RESISTANCE

Antivir Ther. 2007; 12:S40 (abstract no. 35)

C Payan^1,2, P Veillon¹, H Le Guillou-Guillemette¹, C Gaudy³, F Lunel¹ and the Fontevraud Study Group
¹Laboratoire de Virologie-HIFIH, UPRES EA 3859, CHU Angers, France; ²Département de Microbiologie – LBEM EA 3882, Hôpital Morvan, CHU Brest, France; ³Université Francois Rabelais, INSERM ERI 19, Faculté de Médecine, Tours, France

BACKGROUND: HCV NS5A protein has been disputably implicated in the resistance of HCV to IFN therapy in both Japanese and European clinical studies, particularly for HCV genotype 1b.

METHODS: Quasispecies were studied by cloning and sequencing in sequential isolates from 10 patients infected by HCV genotype 1b and treated by 3 months of IFN-α2b alone followed by IFN-α2b alone or combined therapy IFN-R during 9 months. Two groups of patients were studied according to their response to treatment, 7 sustained virological responders (SVR) (150 quasispecies) and 3 non-responders (NR) to IFN-ribavirin (IFN-R) (106 quasispecies). Quasispecies were compared to HCV-J 1b reference strain.

RESULTS: At baseline, SVR patients presented a higher complexity of NS5a quasispecies than NR patients (33.9 versus 29.8 amino acids mutations, P<0.001). Most SVR patients had a decrease of the complexity of quasispecies at 3 months of therapy (31.7, P=0.005,) whereas NR patients were more stable or increased (30.8 mutations). The V3 domain analysis of NS5A protein was able to discriminate SVR from NR patients (6.0 versus 4.7 mutations, P<0.001), with high predictive value.

CONCLUSIONS: These results suggested that detailed molecular analysis of the NS5A protein may be important to understand the resistance to IFN treatment in HCV 1b infection.

This study was supported by a grant from the French ANRS.

2007-06-12
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