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Abstract Details
Treatment failure with DAA therapy: importance of resistance
J Hepatol. 2021 Mar 11;S0168-8278(21)00169-0. doi: 10.1016/j.jhep.2021.03.004.Online ahead of print.
Viral resistance is a major reason for virological failure to direct acting antiviral (DAA) treatment in patients with chronic hepatitis C virus (HCV) infection. However, importance mainly depends on DAA regimen and HCV genotype. For first-line therapy with Glecaprevir/Pibrentasvir (G/P) or Velpatasvir/Sofosbuvir (VEL/SOF) due to the high antiviral activity and high barrier to resistance no general baseline resistance analysis is required. If available, it may help to optimize therapy in certain subgroups of patients with HCV genotype 3 and other rare HCV geno/subtypes. For second-line treatment of DAA-failure patients Voxilaprevir/Velpatasvir/Sofosbuvir (VOX/VEL/SOF) as multiple targeted rescue therapy is the first choice with rates of viral eradication above 90% irrespective of the presence of resistance associated substitutions (RASs). However, in resource-limited settings only first generation DAAs may be available for second line therapy. Here, RASs selected during initial antiviral therapy should be considered if testing is available and rescue treatment should include a switch to a regimen with a new DAA-class to optimize treatment response. For both, VOX/VEL/SOF and rescue therapy with first generation DAAs patients with HCV genotype 3 are overrepresented in the group of treatment failures. Limited data are available for third-line therapies. Here, independent of RASs profiles treatment with G/P plus SOF or VOX/VEL/SOF with or without ribavirin for 12 to 24 weeks showed promising results and should be administered.