Challenges and perspectives of direct antivirals for the treatment of hepatitis C virus infection

Treatment of chronic hepatitis C virus infection has been revolutionised by the development of direct-acting antivirals (DAAs). All-oral, once-daily, 8- to 12-week treatment regimens are now standard of care, with viral eradication possible in >95% of patients across different populations. Despite these advances, several unresolved issues remain, including treatment of patients with hepatitis C virus genotype 3, chronic kidney disease, and those in whom DAA therapy has previously failed. Glecaprevir/pibrentasvir and sofosbuvir/velpatasvir/voxilaprevir are the most recently approved DAA regimens. Given the overwhelming success of modern DAA-based therapies, glecaprevir/pibrentasvir and sofosbuvir/velpatasvir/voxilaprevir are also likely to represent the last DAAs to be approved. Both are pangenotypic, once-daily, all-oral DAA combinations that have the potential to close the gaps in the current DAA treatment portfolio. Herein, we review the challenges associated with current DAAs and how these two regimens may be implemented in existing treatment algorithms.