Containing "The Great Houdini" of viruses: combining direct acting antivirals with the host immune response for the treatment of chronic hepatitis C

Drug Resist Updat. Jul-Nov 2013;16(3-5):60-7. doi: 10.1016/j.drup.2013.06.001. Epub 2013 Aug 2.


Presently the development of new therapies for hepatitis C virus (HCV) is rapidly moving forward. Almost every week new data appear on how direct acting antivirals (DAAs) succeed or fail in clinical trials. Despite the potency of many of the DAA combinations, the effect exerted by ribavirin (RBV) is still needed for an effective therapy in many new DAA combinations. Due to the strong antiviral effect of DAAs, it is likely that a major complementary therapeutic effect exerted by RBV is immune modulation resulting in an increased barrier to development of resistance. For HCV genotype 1a infections elimination of pegylated interferon, is not possible in many DAA combinations without jeopardizing the results. The host immune response is thus likely to play a key role even during DAA-based therapies. Hence, T cells may recognize and eliminate viral variants with resistance to the DAAs. We herein show several examples where this may be the case, supporting the rationale of including the host response also in the new therapeutic regimens. This review will describe the potential benefits of combining various DAAs with means to activate the specific immune response against HCV.

Keywords: DNA vaccine; Electroporation; HCV; T cell; Therapeutic vaccine.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Neutralizing / therapeutic use
  • Antibodies, Viral / therapeutic use
  • Antiviral Agents / therapeutic use*
  • Combined Modality Therapy
  • Drug Resistance, Viral
  • Hepacivirus / drug effects*
  • Hepacivirus / immunology
  • Hepacivirus / metabolism
  • Hepatitis C, Chronic / immunology
  • Hepatitis C, Chronic / metabolism
  • Hepatitis C, Chronic / therapy*
  • Hepatitis C, Chronic / virology
  • Humans
  • Immunomodulation / drug effects*
  • Ligands
  • Models, Biological*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / metabolism
  • Ribavirin / therapeutic use
  • Toll-Like Receptors / agonists
  • Toll-Like Receptors / metabolism
  • Viral Hepatitis Vaccines / therapeutic use


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antiviral Agents
  • Ligands
  • Programmed Cell Death 1 Receptor
  • Toll-Like Receptors
  • Viral Hepatitis Vaccines
  • Ribavirin