Overview of direct-acting antiviral drugs

Direct-acting antiviral drugs for hepatitis C virus (HCV) infection were first approved by the Therapeutic Goods Administration (TGA) in Australia in 2015 and are available through the Pharmaceutical Benefits Scheme (PBS)¹. Direct-acting antiviral regimens are highly effective and well tolerated, and replace older interferon-based therapies. Treatment with one of the pangenotypic regimens consists of one or three tablets taken daily, for a duration of 8 to 12 weeks.

Over 95% of patients who adhere to treatment will be cured with direct-acting antiviral drug therapy (cure rates are lower in patients with advanced cirrhosis, especially with HCV genotype 3). Failure to achieve a cure is usually a result of nonadherence, drug resistance or reinfection.

Combinations of antiviral drugs from different classes are used to target multiple steps in the hepatitis C virus life cycle. These include NS5B nucleotide inhibitors (eg sofosbuvir), NS5A inhibitors (eg velpatasvir, pibrentasvir, elbasvir, ledipasvir) and NS3/4A protease inhibitors (eg glecaprevir, grazoprevir, voxilaprevir). Some combinations of direct-acting antivirals are pangenotypic (effective against genotypes 1 to 6 of hepatitis C) while others are only effective for specific genotypes. At the time of writing there are three pangenotypic combinations available in Australia—two are used in treatment-naive patients, and one is used for those who have not been cured with a first-line regimen due to virological failure.