Advances in the treatment of hepatitis C virus infection

Since 2007, the annual age-adjusted mortality rate in hepatitis C virus (HCV) infection in the United States has been greater than that in HIV disease, reflecting the continuing decline in HIV-related mortality and the continuing increase in HCV-related mortality. The approval of 2 new direct-acting antivirals within the past year, as well as the promise offered by numerous other direct-acting agents in development, provides hope that we will be able to markedly improve our ability to cure HCV disease. The addition of a protease inhibitor (PI) to what has been the standard HCV therapy of peginterferon alfa and ribavirin dramatically improves sustained virologic response rates in treatment-naive patients with genotype 1 infection. Similar results have been observed in some treatment-experienced patients in whom prior peginterferon alfa/ribavirin therapy has failed. The use of these new agents has also permitted response-guided therapy, wherein early sustained virologic response to treatment allows for a shortened treatment duration. However, these new PIs add cost and adverse effects to HCV therapy. Boceprevir is associated with increased risk of anemia and dysgeusia, and telaprevir is associated with increased risk of anemia and skin and gastrointestinal adverse effects. Early studies indicate that the addition of PIs results in high response rates in patients with HCV/HIV coinfection. Other studies suggest that combinations of PIs and other direct-acting antivirals may ultimately permit cure when used in interferonsparing regimens.