The pharmacology, pharmacokinetics, interaction potential, efficacy, and safety of the newest direct-acting antiviral (DAA) medication for the treatment of chronic hepatitis C are reviewed.Summary
Nonstructural proteins 5A (NS5A) and 5B (NS5B) are key drivers of hepatitis C virus (HCV) replication. Velpatasvir, an inhibitor of NS5A, was coformulated with the NS5B inhibitor sofosbuvir to provide a single-tablet combination DAA (Epclusa, Gilead Sciences). Sofosbuvir–velpatasvir was shown to have excellent activity against the 6 most prevalent HCV genotypes in the United States, with reported rates of sustained virological response at 12 weeks after treatment completion ranging from 95% to 100% in various HCV-infected populations, including patients with compensated cirrhosis and prior treatment failures. In patients with decompensated cirrhosis or HIV coinfection, reported cure rates are 85–100% and 92–100%, respectively. The duration of treatment with sofosbuvir–velpatasvir is 12 weeks regardless of the HCV genotype involved, previous treatment, and the presence of cirrhosis or baseline resistance-associated NS5A mutations. In patients with decompensated cirrhosis, sofosbuvir–velpatasvir must be used in combination with ribavirin. Sofosbuvir–velpatasvir was well tolerated in clinical trials; adverse effects reported at a rate of ≥10% were fatigue, headache, nausea, and nasopharyngitis.Conclusion
Sofosbuvir–velpatasvir is a DAA and the first single-tablet regimen to treat HCV infection caused by all genotypes. The efficacy and tolerability of sofosbuvir–velpatasvir have been observed in patients with types of HCV infection that traditionally have been difficult to treat.