title: The hepatitis C revolution part 2: difficult-to-treat groups and experimental approaches.
abstract: OBJECTIVE
  Novel direct-acting antiviral (DAA) agents are highly effective in the treatment of hepatitis C, achieving unprecedented rates of sustained virological response, a functional cure. However, a significant minority of patients belong to 'difficult-to-treat' groups, in which efficacy of DAAs appears less robust. The review article aims to discuss additional treatment strategies which may be employed in these patient cohorts, as well as evidence for the potential role of experimental DAAs.
  
  
  RESULTS
  Patients with genotype 3 infection have consistently lower rates of virological clearance following DAA therapy when compared with other genotypes. However, in combination with sofosbuvir, the novel nonstructural protein 5A inhibitor daclatasvir has demonstrated high efficacy in the treatment of noncirrhotic genotype 3 infection. Recent data from phase 2 and 3 clinical studies support the use of currently approved DAA regimens in the treatment of patients with hepatitis C virus and human immunodeficiency virus (HIV) coinfection. Sustained virological response rates in coinfected patients are analogous to those observed in monoinfection, such that HIV infection itself does not pose a barrier to DAA efficacy. In posttransplant populations, DAAs have again shown great potential, with trial data validating use of sofosbuvir/ledipasvir.
  
  
  CONCLUSIONS
  Unmet need persists in certain subsets of the hepatitis C patient population. The arrival on scene of novel DAAs is likely to further expand the repertoire of available therapy for these 'difficult-to-treat' groups.
authors.affiliation: Nottingham University Hospitals NHS Trust and NIHR Biomedical Research Unit and the University of Nottingham Digestive Diseases Centre, Queens Medical Centre, Nottingham, UK.
authors.forename: Prarthana
authors.initials: P
authors.lastname: Thiagarajan
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Ryder
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D060085:Coinfection; D015195:Drug Design; D024882:Drug Resistance, Viral / Q000187:drug effects*; D005449:Fluorenes / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D016174:Hepacivirus / Q000187:drug effects*; D006526:Hepatitis C / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D006801:Humans; D000069474:Sofosbuvir; D014542:Uridine Monophosphate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D005449:Fluorenes; C000595958:ledipasvir, sofosbuvir drug combination; D014542:Uridine Monophosphate; D000069474:Sofosbuvir