What future for ribavirin?
The optimal therapy for patients with the chronic hepatitis C virus (HCV) is a combination of peginterferon and ribavirin. Treating HCV without ribavirin or prematurely discontinuing, frequently missing doses of ribavirin is associated with a significant decline in virological response, and an increase in both breakthrough viraemia and relapse. The major limitation of ribavirin is adverse events, the most common of which is haemolytic anaemia. Haemolysis is modest when ribavirin is utilized as monotherapy, but is significantly increased when combined with interferon or peginterferon. For these reasons, attempts to replace ribavirin with a less toxic alternative have been advanced. Unfortunately, even when ribavirin is replaced by a potent protease inhibitor, relapse is significantly increased and SVR is reduced. The future of HCV treatment is to combine peginterferon and ribavirin with several protease and/or polymerase inhibitors. Whether this strategy will allow ribavirin to be removed from the treatment paradigm remains to be proven. However, based on the results of clinical trials conducted to date, it is much more likely that peginterferon, not ribavirin, could be expendable.
Shiffman
Mitchell L
ML
Hepatology Section, Virginia Commonwealth University Medical Center, Richmond, VA 23298, USA. mshiffma@vcu.edu
D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D016174:Hepacivirus / Q000187:drug effects*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D011480:Protease Inhibitors / Q000627:therapeutic use*; D012254:Ribavirin / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012324:RNA-Dependent RNA Polymerase
D000998:Antiviral Agents; D011480:Protease Inhibitors; D012254:Ribavirin; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase