An update on direct antiviral agents for the treatment of hepatitis C

ABSTRACT

Introduction: The development of direct-acting antiviral (DAA) agents for the treatment of hepatitis C virus (HCV) infection has completely transformed the management of this disease. The advantages of using DAA therapies include high efficacy (sustained virological response (SVR) rate >95%) with minimal side effects, good tolerability, easy drug administration (once daily oral dosing), and short duration of treatment (8–12 weeks). This transformative nature of DAA therapy underpins the goal of the World Health Organization to eliminate HCV infection as a public health threat by 2030.

Areas covered: This review seeks to address the current status of DAA therapies, including recent developments, current limitations, and future challenges.

Expert opinion: The current DAA regimens, with their high effectiveness and safety profiles, have changed patient perception of HCV infection from a disease that requires complex evaluation and long-term monitoring to a disease that can be cured after one visit to the general practitioner. Despite the remarkably high success rate of DAAs, few patients (4–5%) fail to obtain SVR even after treatment. Five years ahead, the landscape of HCV treatment will undoubtedly continue to evolve, and more pan-genotypic treatment options will be available to all patients.

KEYWORDS:

• Direct-acting antiviral agents
• hepatitis C virus
• recent developments
• remaining challenges

Article highlights

• DAAs have completely changed the treatment paradigm for HCV infection

• The complex life cycle of HCV provides several types of treatment targets that are involved in viral suppression.

• The pan-genotypic DAA combinations are highly effective across all genotypes, even in patients that were previously considered to be ‘hard to treat’, with good safety profiles and short treatment durations.

• Generic DAAs may represent valuable alternatives in limited-resource countries.

• DAA failures (~5%) are mainly related to virological failure caused by resistance-associated variants, which have been reported for all DAAs. SOF/velpatasvir±voxilaprevir (SOF/VEL±VOX) or glecaprevir/pibrentasvir (GLE/PIB) are the only options currently available for re-treatment.

The development of DAA therapy opened the door to a very ambitious goal—the elimination of HCV by 2030.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.