Ombitasvir and paritaprevir boosted with ritonavir and combined with dasabuvir for chronic hepatitis C.
Hepatitis C is a leading cause of cirrhosis and hepatocellular carcinoma responsible for almost 700,000 deaths worldwide annually. Until 2014, management of HCV infections was based on interferon alfa containing regimens, with efficacy of 40-70% and a high adverse event rate. Interferon-free therapeutic options improved sustained viral response (SVR) rate to >90% and safety profile to placebo-like levels. Areas covered: This article describes all-oral regimen consisting of three direct acting antivirals (DAA) - ombitasvir (OBV), paritaprevir (PTV) and dasabuvir (DSV), which in clinical practice is boosted with ritonavir (r) and sometimes with ribavirin (RBV). This combination is registered for treatment of patients infected with HCV genotype 1 and 4. We focused on the regimen characteristics, pharmacokinetics, risk of resistance as well as efficacy and safety in clinical trials and real world studies. Expert commentary: Combination of OBV/PTV/r±DSV±RBV provides SVR rate of about 95% and good safety profile even in patients with compensated liver cirrhosis and failure with previous therapy. Currently it should be of particular value in areas with a predominance of genotype 1b infections. Due to the complexity and risk of drug to drug interactions, it will probably be replaced in coming few years with pangenotypic combinations of next generation DAAs.
a Department of Infectious Diseases and Hepatology , Medical University of Białystok , Białystok , Poland.
Robert
R
Flisiak
b Department of Pediatrics, Gastroenterology and Allergology , Medical University of Białystok , Białystok , Poland.
Marta
M
Flisiak-Jackiewicz
D015081:2-Naphthylamine; D000284:Administration, Oral; D000813:Anilides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002219:Carbamates / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D003521:Cyclopropanes; D004338:Drug Combinations; D004347:Drug Interactions; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D011392:Proline / Q000031:analogs & derivatives; D019438:Ritonavir / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D013449:Sulfonamides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000072230:Sustained Virologic Response; D016896:Treatment Outcome; D014498:Uracil / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D014633:Valine
D000813:Anilides; D000998:Antiviral Agents; D002219:Carbamates; D003521:Cyclopropanes; D004338:Drug Combinations; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds; D013449:Sulfonamides; C586094:ombitasvir; D014498:Uracil; D011392:Proline; D015081:2-Naphthylamine; C588260:dasabuvir; D014633:Valine; D019438:Ritonavir; C585405:paritaprevir
HCV; Viral hepatitis; dasabuvir; direct-acting antivirals; ombitasvir; paritaprevir