Naturally occurring substitutions conferring resistance to hepatitis C virus polymerase inhibitors in treatment-naive patients infected with genotypes 1-5 - Archive ouverte HAL Access content directly
Journal Articles Antiviral Therapy Year : 2009

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

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Abstract

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.

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Dates and versions

hal-03268565 , version 1 (23-06-2021)

Identifiers

  • HAL Id : hal-03268565 , version 1
  • OKINA : ua3543

Cite

Florence Abravanel, Cécile Henquell, Hélène Le Guillou-Guillemette, Viorica Balan, Audrey Mirand, et al.. Naturally occurring substitutions conferring resistance to hepatitis C virus polymerase inhibitors in treatment-naive patients infected with genotypes 1-5. Antiviral Therapy, 2009, 14 (5), pp.723 - 730. ⟨hal-03268565⟩
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