VEILLON P, PAYAN C, LUNEL-FABIANI F; and the Fontevraud Study Group; Interscience Conference on Antimicrobial Agents and Chemotherapy (43rd: 2003: Chicago, Ill.).

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2003 Sep 14-17; 43: abstract no. V-781.

CHU Angers, Angers, France.

BACKGROUND: The hepatitis C virus (HCV) nonstructural 5A (NS5A) has been controversially implicated in the resistance of HCV to Interferon (IFN) therapy in clinical studies. In Japan, mutations in IFN sensitivity-determining region (ISDR) (aa 2209-2248) in the NS5A gene was associated with response to IFN therapy in patients infected with genotype 1b. In contrast, studies from Europe did not confirm such association. More recently, it has been suggested that the V3 domain (aa 2353-2379) outside the putative ISDR may also have amino acids changes that may be associated with response to IFN. In this study, the relationship between NS5A mutations in ISDR and V3 domains and virological response to therapy was investigated. METHODS: The NS5A gene was sequenced from 35 HCV genotype 1b infected patients, in a prospective clinical trial of IFN therapy and IFN plus Ribavirin combination therapy at D0, M3 and M6. RESULTS: In the ISDR domain, we did not observed significantly different variations in amino acids between responders (1.52 +/- 1.75, n= 21, range 0-6) and non-responders (1.07 +/- 0.83, n= 14, range 0-3), (p= 0.778), to therapy when tested before the beginning of treatment. In the V3 domain, we found more mutations in responders (6.48 +/- 1.86, n= 21, range 2-11) than in non-responders (4.71 +/- 1.20, n= 14, range 3-8), before the beginning of treatment, (p= 0.001). Few variations were observed during treatment in non-responders (1.38 +/- 1.51, n= 8, range 0-4) but the number of substitutions in responders to combination therapy were more important (6.60 +/- 4.51, n= 5, range 1-13), after three months of treatment (p= 0.019). CONCLUSIONS: Our results confirm that, in Europe, the sequence of the ISDR domain of HCV was not predictive for treatment success. However, we found that the V3 domain have greater variability in responders than non-responders suggesting that this V3 domain needs further investigation.

Publication Types:

• Meeting Abstracts

Keywords:

• Base Sequence
• Europe
• Genotype
• Hepacivirus
• Humans
• Interferon Alfa-2b
• Interferons
• Japan
• Longitudinal Studies
• Mutation
• Ribavirin
• genetics

Other ID:

• GWAIDS0025594

UI: 102265218

From Meeting Abstracts