title: Ledipasvir : a novel synthetic antiviral for the treatment of HCV infection.
abstract: BACKGROUND
  About 150,000,000 people worldwide are chronically infected with hepatitis C virus (HCV). HCV infection can lead to liver cirrhosis, hepatocellular carcinoma and death. Treatment was based previously only on pegylated interferon combined with other antiviral drugs. Recently, the first interferon-free combination for patients with genotype 2 or 3 was approved in the USA and Europe, and several molecules are in an advanced phase of clinical development.
  
  
  METHODS
  This review focuses on the pharmacokinetics, pharmacodynamics and tolerability of ledipasvir , an inhibitor of HCV nonstructural 5A protein. The authors also highlight the drug's safety and resistance profile.
  
  
  CONCLUSIONS
  The pharmacokinetic profile and antiviral activity of ledipasvir are ideal. However, given the high rate of natural and drug-related ledipasvir-resistant HCV mutations, ledipasvir is administered in combination regimens with other antiviral drugs, which resulted in a cure rate up to 100%. While ledipasvir is effective in patients with genotype 1 chronic hepatitis C, its efficacy remains to be established in patients with genotype 4, 5 or 6, in subjects with HIV coinfection, in hemodialyzed and elderly patients and in subjects with decompensated cirrhosis. If the excellent results of combination therapy be confirmed in larger trials, hepatologists will have the possibility to cure most HCV-positive patients in the near future.
authors.affiliation: University of Naples "Federico II", Department of Clinical Medicine and Surgery , via S. Pansini 5, I-80131 Naples , Italy +39 081 746 3178 ; +39 081 746 3190 ; ivan.gentile@unina.it.
authors.forename: Ivan
authors.initials: I
authors.lastname: Gentile
authors.forename: Antonio Riccardo
authors.initials: AR
authors.lastname: Buonomo
authors.forename: Federico
authors.initials: F
authors.lastname: Borgia
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Castaldo
authors.forename: Guglielmo
authors.initials: G
authors.lastname: Borgia
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005449:Fluorenes / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D005449:Fluorenes; D016898:Interferon-alpha; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D017361:Viral Nonstructural Proteins; C586541:ledipasvir; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C100416:peginterferon alfa-2a