Naturally occurring substitutions conferring resistance to hepatitis C virus polymerase inhibitors in treatment-naive patients infected with genotypes 1-5

TitreNaturally occurring substitutions conferring resistance to hepatitis C virus polymerase inhibitors in treatment-naive patients infected with genotypes 1-5
Type de publicationArticle de revue
AuteurAbravanel, Florence, Henquell, Cécile, Le Guillou-Guillemette, Hélène, Balan, Viorica, Mirand, Audrey, Dubois, Martine, Lunel-Fabiani, Françoise , Payan, Christopher, Izopet, Jacques
EditeurInternational Medical Press
TypeArticle scientifique dans une revue à comité de lecture
Année2009
LangueAnglais
Date2009
Numéro5
Pagination723 - 730
Volume14
Titre de la revueAntiviral therapy
ISSN1359-6535
Mots-clésAmino Acid Substitution, Antiviral Agents, Drug Resistance, Viral, Genotype, Hepacivirus, Hepatitis C, Humans, Prevalence, RNA Replicase, Sequence Analysis, DNA, Viral Nonstructural Proteins
Résumé en anglais

BACKGROUND: The hepatitis C virus (HCV) RNA-dependent RNA polymerase, NS5B, is essential for virus RNA replication. It is thus an attractive therapeutic target. Several compound nucleoside analogues, non-nucleoside inhibitors and cyclosporine analogues are being developed to inhibit NS5B activity. However, nucleotide changes in the NS5B gene can confer resistance to them.METHODS: We investigated the prevalence of known substitutions conferring resistance in HCV polymerase in 124 treatment-naive French patients infected with HCV genotypes 1, 2, 3, 4 or 5 by sequencing the NS5B gene. RESULTS: None of the 124 HCV NS5B sequences analysed contained substitutions conferring resistance to nucleoside analogues; however, NS5B polymerases containing substitutions conferring resistance to non-nucleoside inhibitors were frequent within genotype 1 strains (17%) and very common in non-genotype 1 strains. Similarly, substitutions conferring resistance to cyclosporine analogues were more prevalent within the various genotypes. CONCLUSIONS: Naturally occurring substitutions conferring resistance to NS5B inhibitors are common in treatment-naive patients infected with HCV genotype 1, 2, 3, 4 or 5. Their influence on treatment outcome should be assessed.

URL de la noticehttp://okina.univ-angers.fr/publications/ua3543