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The importance of resistance to direct antiviral drugs in HCV infection in clinical practice

Published:September 24, 2015DOI:https://doi.org/10.1016/j.jhep.2015.09.011

      Summary

      Treatment of chronic hepatitis C virus (HCV) infection with direct-acting antiviral agents (DAA) is associated with high rates of sustained virologic response. Remaining factors associated with treatment failure include advanced stages of liver fibrosis, response to previous antiviral therapy and viral factors such as baseline viral load and suboptimal interaction of the DAA with the target based on viral variants. Heterogeneity within NS3, NS5A, and NS5B areas interacting with DAAs exist between HCV geno- and subtypes as well as HCV isolates of the same geno- and subtype and amino acid polymorphisms associated with suboptimal efficacy of DAAs are termed resistance-associated variants (RAVs). RAVs may be associated with virologic treatment failure. However, virologic treatment failure typically occurs only if other negative predictive host or viral factors are present at the same time, susceptibility to additional antiviral agents is reduced or duration of treatment is suboptimal. In this review geno- and phenotypic resistance testing as well as clinical data on the importance of RAVs for conventional triple therapies with sofosbuvir, simeprevir, and daclatasvir and available interferon-free DAA combinations are discussed.

      Abbreviations:

      HCV (hepatitis C virus), DAA (direct-acting antiviral agent), NS3 (non-structural protein 3), NS5A (non-structural protein 5A), NS5B (non-structural protein 5B), RAVs (resistance associated variants), IP-10 (interferon-gamma-inducible protein 10), IFNL4 (interferon lambda 4), IL28B (interleukin 28B), HIV (human immunodeficiency virus), HBV (hepatitis B virus), PEG/R (pegylated interferon plus ribavirin), PI (protease inhibitor), SVR (sustained virological response), EC50 (half maximal effective concentration), die (Latin: dies, day), IU (international unit), GT (genotype), TID (Latin: ter in die, three times daily), QD (Latin: quaque die, once daily), BID (Latin: bis in die, twice daily), IC50 (half maximal inhibitory concentration), PEG-IFN (pegylated interferon), BOC (boceprevir), TVR (telaprevir), SMV (simeprevir), DCV (daclatasvir), ASV (asunaprevir), SOF (sofosbuvir), PTV/r (ritonavir-boosted paritaprevir), OMV (ombitasvir), DSV (dasabuvir), ISG (interferon-stimulated genes), TN (treatment naive), TE (treatment-experienced), R (ribavirin), bl (baseline), pts (patients)

      Keywords

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