Protease inhibitors for the treatment of chronic hepatitis C genotype-1 infection: the new standard of care.
For the past decade, the standard treatment for chronic hepatitis C infection has been pegylated-interferon plus ribavirin. With US Food and Drug Administration approval of boceprevir and telaprevir--two protease inhibitors--the standard-of-care treatment for genotype-1 infection, the main genotype worldwide, is now peginterferon plus ribavirin and a protease inhibitor. Rates of sustained virological response or cure with triple combination treatment have improved substantially, both in patients who have had previous treatment and in those who have not. Improvements have been most substantial in populations regarded as difficult to treat, such as individuals with cirrhosis. However, despite improved response rates, protease inhibitors have incremental toxic effects, high costs, increased pill burden, and many drug interactions. Moreover, because new antiviral drugs directly inhibit hepatitis C virus, viral resistance has become an important issue, essentially precluding use of protease inhibitor monotherapy, and potentially restricting future treatment options for patients who consequently do not achieve sustained virological response. Protease inhibitors are the first of many antiviral medications that will probably be combined in future interferon-free regimens.
Center for Hepatitis C, Atlanta Medical Center, Atlanta, GA 30309, USA. brianpearlman@hotmail.com
Brian L
BL
Pearlman
D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D005838:Genotype; D016174:Hepacivirus / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011392:Proline / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D011480:Protease Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011994:Recombinant Proteins / Q000008:administration & dosage; D012254:Ribavirin / Q000008:administration & dosage; D059039:Standard of Care / Q000639:trends*; D014481:United States
D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D011480:Protease Inhibitors; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; D011392:Proline; C100416:peginterferon alfa-2a