Novel drugs in the management of difficult-to-treat hepatitis C genotypes

BACKGROUND: Hepatitis C virus (HCV) infection is the most common chronic bloodborne infection in the United States, with approximately 3.2 million Americans being chronically infected. Rates of HCV-related end-stage liver disease and its associated morbidity and mortality have yet to peak, so there is a pressing need for more effective and tolerable HCV treatment. HCV genotypes 1, 4, 5, and 6 are considered difficult to treat, and the need for improved therapies is especially great for persons infected with these genotypes. CURRENT STRATEGIES FOR HCV TREATMENT: Current therapy for genotype 1 HCV infection includes triple therapy with pegylated interferon, ribavirin, and a NS3/4A protease inhibitor. Sustained virologic response (SVR) rates with triple therapy range from 42% to 75%, a vast improvement over pegylated interferon and ribavirin therapy alone. However, response rates remain suboptimal, and triple therapy is associated with significant adverse effects and is only indicated for genotype 1 HCV infection. NOVEL DRUGS FOR HCV TREATMENT: HCV drug development is proceeding at a rapid pace to meet this need. Novel direct acting antiviral agents in several classes, including new NS3/4A serine protease inhibitors, NS5A replication complex inhibitors, NS5B polymerase inhibitors, interferon lambda, and microRNAs, are in varying stages of development. These new therapeutic agents promise SVR rates of up to 100% with durations as short as 12 weeks and, often, fewer adverse effects. CONCLUSION: New drug development in HCV is proceeding at an unprecedented pace. Novel agents promise higher SVR rates, shorter duration of therapy, and fewer adverse effects than have been possible with HCV therapy to date.