Role of ledipasvir/sofosbuvir combination for genotype 1 hepatitis C virus infection

Abstract

Chronic hepatitis C virus (HCV) infection is one of the most common etiologies of liver-related mortality throughout the world. Among the six HCV genotypes, genotype 1 was significantly more aggressive when utilizing the combination of pegylated interferon and ribavirin, as genotype 1-infected patients had the lowest likelihood of achieving cure (40%–50%) and required twice as long duration of treatment, as compared to genotypes 2 and 3. Recently, however, significant advances have been made with the advent of all-oral direct-acting antiviral agents, which have significantly improved the safety, efficacy, and tolerability of the treatment of HCV genotype 1. Among the available treatments for HCV genotype 1, the combination therapy of ledipasvir/sofosbuvir provides several advantages compared to other regimens, including use of a single-pill regimen, possibility to shorten the duration of treatment to 8 weeks, efficacy in patients exposed to protease inhibitors, safety in decompensated cirrhosis, and potential to avoid ribavirin. In this review, we discuss the pharmacotherapy of the combination of ledipasvir/sofosbuvir therapy and summarize the results of the Phase III clinical trials for this treatment in HCV genotype 1 patients. We will also discuss the data for special populations, including decompensated cirrhosis, human immunodeficiency virus (HIV) coinfected patients, African-Americans, the elderly, and those who failed sofosbuvir-containing regimens.

Keywords:

• pegylated interferon
• ribavirin
• cirrhosis
• liver transplantation
• direct-acting antiviral

Author contributions

VS and KVK both contributed equally to conceptualization and study design, including literature search, and drafting and critical revision of the manuscript. Both authors are guarantors. All authors contributed toward data analysis, drafting and revising the paper and agree to be accountable for all aspects of the work.

Disclosure

VS: Speaker’s bureau: Salix, Gilead, Abbvie, BMS, Intercept. Advisory board: Gilead, Abbvie, Janssen, BMS, Intercept. KVK: Grants/Research: Evidera, Gilead, Immuron, Intercept, Tobira. Advisory board: Abbvie, Achillion, BMS, Evidera, Gilead, Merck, Novartis, Trio Health. Consultant: Abbvie, Gilead. The authors report no other conflicts of interest in this work.