title: Dasabuvir (ABT333) for the treatment of chronic HCV genotype I: a new face of cure, an expert review.
abstract: Hepatitis C virus (HCV) affects nearly 1.3% of US population and around 2% of people worldwide. It is associated with serious complication of Cirrhosis and Hepatocellular carcinoma leading to significant morbidity and mortality. Until now the only treatment option for this serious disease was interferon based therapy which had poor tolerance and at best SVR (Sustained virological response) in only 50% of cases. With the introduction of other direct - acting antiviral agents the treatment of HCV has been revolutionized with significantly high rates of cure. Among novel Direct acting antivirals are non-nucleoside inhibitor NS5B which is highly effective in treatment of HCV genotype 1 a and 1b including those with compensated cirrhosis achieving high cure rates with SVR more than 97 % in pooled analysis from six different phase 3 trials. This review will discuss the DAA - Dasabuvir, a non - nucleoside NS5B inhibitor, its mechanism of action, efficacy, safety & tolerance, and drug resistance. Dasabuvir is approved by FDA in combination with other DAA agents called as the 3D(Viekira Pak) in various interferon free regimens achieving high cure rates (SVR >95%) with low adverse effects. In Europe, it is approved by European medicines agency for use in combination with Ombitasvir, Paritaprevir, and ritonavir with or without ribavirin. The drug is used in treatment naive as well as previously treated patient with high success rates. It is also approved in patients with compensated cirrhosis, patients with HIV co-infection and liver transplant recipients which were in the past were excluded from treatment with interferon based therapy. Dasabuvir is extensively evaluated in large clinical trials and shown excellent SVR among HCV genotype1 patient population in combination with other oral DAAs, with good safety profile and tolerance. Its drawback is its genotype restriction, need for ribavirin (RBV) for 1a genotype, low resistance barrier and high cost. It is well tolerated with less than 1 % of patients permanently discontinuing treatment and 2% of patient experiencing a serious adverse reaction. It is contraindicated in patients with known hypersensitivity to ritonavir (e.g. Steven - Johnson syndrome) and strong inducers of CYP3A and CYP2CB.
authors.affiliation: a Research and Hepatobiliary Tumor Program , The Liver Institute at Methodist Dallas Medical Center.
authors.forename: Parvez S
authors.initials: PS
authors.lastname: Mantry
authors.affiliation: b Department of Internal Medicine , Methodist Dallas Medical Center.
authors.forename: Lakshmikant
authors.initials: L
authors.lastname: Pathak
mesh_terms: D015081:2-Naphthylamine; D000998:Antiviral Agents / Q000627:therapeutic use*; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D047028:Macrocyclic Compounds / Q000627:therapeutic use*; D012254:Ribavirin / Q000627:therapeutic use*; D019438:Ritonavir / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D014498:Uracil / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D004338:Drug Combinations; D047028:Macrocyclic Compounds; D013449:Sulfonamides; C000607373:Viekira Pak; D012254:Ribavirin; D014498:Uracil; D007372:Interferons; D015081:2-Naphthylamine; C588260:dasabuvir; D019438:Ritonavir
keywords: 3D; ABT 333; ABT-450; Dasabuvir; HCV; direct antiviral agents (DAA); polymerase inhibitor; sustained virological response (SVR)