title: Sofosbuvir for the treatment of hepatitis C virus.
abstract: BACKGROUND
  The current treatment for hepatitis C virus (HCV) genotype 1 chronic infection is the addition of direct-acting antivirals (DAAs) with a protease inhibitor (telaprevir or boceprevir) to the pegylated interferon (PEG-IFN) and ribavirin (RBV) regimen. In 2014, sofosbuvir, simeprevir and faldaprevir may be available, each in combination with PEG-IFN/RBV triple therapy. All the HCV enzymes are essential for HCV replication, and are potential drug discovery targets. Therefore, DAAs with different viral targets, including NS3 protease inhibitors, nucleoside/nucleotide analogue and nonnucleoside inhibitors of the RNA-dependent RNA polymerase, and NS5A replication complex inhibitors are under development.
  
  
  METHODS
  Interestingly, several IFN-free Phase III trials are ongoing with promising results. Among DAAs, sofosbuvir is a potent HCV-specific nucleotide analog (chain terminator). The aim of this article is to review sofosbuvir data, in particular Phase III trials.
  
  
  CONCLUSIONS
  Sofosbuvir has a high barrier to resistance with no virologic breakthrough to date. It has a pan-genotypic activity (even though lower rates of response for genotype 3). So far, no safety signal in preclinical/clinical studies has been observed with this compound. It is given orally, once daily, without food effect. Sofosbuvir will first be available in association with PEG-IFN/RBV. Sofosbuvir appears to be a key compound and a backbone for future IFN free treatment regimen.
authors.affiliation: Université Paris Diderot-Paris 7, Assistance Publique-Hôpitaux de Paris, Hôpital Beaujon, Centre de Recherche Biomédicale Bichat-Beaujon CRB3, Service d'Hépatologie, Inserm Unité 773 , 100 Bd du Général Leclerc, 92110, Clichy and Paris , France +33 0 140875579 ; +33 0 147309440 ; tarik.asselah@bjn.aphp.fr.
authors.forename: Tarik
authors.initials: T
authors.lastname: Asselah
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors; D016174:Hepacivirus / Q000187:drug effects / Q000502:physiology; D006526:Hepatitis C / Q000188:drug therapy*; D000069474:Sofosbuvir; D014542:Uridine Monophosphate / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018406:Virus Physiological Phenomena
chemical_list: D000998:Antiviral Agents; D014542:Uridine Monophosphate; D012321:DNA-Directed RNA Polymerases; D000069474:Sofosbuvir