New direct-acting antivirals in hepatitis C therapy: a review of sofosbuvir, ledipasvir, daclatasvir, simeprevir, paritaprevir, ombitasvir and dasabuvir

ABSTRACT

Hepatitis C is a chronic infection associated with considerable morbidity and mortality. In recent years, there has been a shift in treatment paradigm with the discovery and approval of agents that target specific proteins vital for hepatitis C replication. The NS3/4A inhibitors simeprevir and paritaprevir, the NS5A inhibitors ombitasvir, ledipasvir, and daclatasvir, and the NS5B inhibitors sofosbuvir and dasabuvir have been newly FDA approved and incorporated as first-line agents into the latest IDSA-AASLD guidelines for Hepatitis C treatment. Used in combination, these agents produce higher rates of sustained virologic response and less adverse effects than historical options, along with limited rates of resistance. Pertinent clinical data, pharmacology, and pharmacokinetics are reviewed for these new direct acting antiviral agents.

KEYWORDS:

• Hepatitis C
• sustained virologic response
• virologic relapse
• sofosbuvir
• ledipasvir
• simeprevir
• daclatasvir
• dasabuvir
• ombitasvir
• paritaprevir

Financial & competing interests disclosure

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.

Key issues

• Knowledge of the hepatitis C virus (HCV) life cycle has prompted the discovery of target-specific direct-acting antiviral (DAA) medications.

• New DAA medications offer safer, oral options with higher rates of SVR compared to older protease inhibitors, ribavirin, and interferon.

• Many DAA formulations inhibit hepatic enzymes to some degree, so pharmacists must be aware of the potential for drug interactions.

• Sofosbuvir has pangenotypic efficacy with low rates of resistance in clinical trials and can be used as a first-line option with ledipasvir, ribavirin, or simeprevir.

• Viekira Pak® is a combination of drugs from three different protease inhibitor classes combined with the pharmacokinetic booster ritonavir.

• Ledipasvir is an NS5A inhibitor, which is currently used only as a combination tablet with sofosbuvir, is a viable treatment option for patients with HCV genotype 1 with or without cirrhosis.

• The DAAs have low rates of adverse effects in clinical trials, especially when used without ribavirin or interferon therapy.

• The main drawback to therapy with new antiviral agents is the high cost currently associated with their use.