Sofosbuvir and ABT-450: terminator of hepatitis C virus?

World J Gastroenterol. 2013 Jun 7;19(21):3199-206. doi: 10.3748/wjg.v19.i21.3199.

Abstract

Combination therapy with peginterferon (pegIFN)-α and ribavirin (RBV) has been the standard of care (SOC) for chronic hepatitis C. Unfortunately, not all patients can achieve a sustained virologic response (SVR) with this regimen. SVR rates are approximately 80% in patients with hepatitis C virus (HCV) genotype 2, 3, 5 and 6 and 40%-50% in patients with genotype 1 and 4. Therefore, strategies to improve SVR rates have been an important issue for clinical physicians. Several direct acting antiviral agents (DAAs) have significantly higher SVR rates when combined with pegIFN-α and RBV than pegIFN-α and RBV alone. Treatments containing DAAs have several advantages over the previous SOC, including higher specificity and efficacy, shorter treatment durations, fewer side effects, and oral administration. Based on these advantages, treatment with pegIFN-α and RBV plus telaprevir or boceprevir has become the current SOC for patients with genotype 1 HCV infection. However, many patients are either not eligible for therapy or decline treatment due to coexisting relative or absolute contraindications as well as an inability to tolerate the hematological side effects and adverse events caused by the new SOC. These factors have contributed to the advent of pegIFN-α-free regimens. The newest therapeutic regimens containing sofosbuvir and ABT-450 have shown promising results. In this review, we summarize the development of anti-HCV agents and the clinical efficacy of sofosbuvir and ABT-450-based therapies as well as the potential for future HCV studies.

Keywords: ABT-450; Antiviral therapy; Hepatitis C virus; Sofosbuvir; Sustained virologic response.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Cyclopropanes
  • Drug Therapy, Combination
  • Genotype
  • Hepatitis C, Chronic / diagnosis
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / genetics
  • Hepatitis C, Chronic / immunology
  • Hepatitis Viruses / drug effects*
  • Hepatitis Viruses / genetics
  • Hepatitis Viruses / growth & development
  • Humans
  • Interferons
  • Interleukins / genetics
  • Lactams, Macrocyclic
  • Macrocyclic Compounds / adverse effects
  • Macrocyclic Compounds / therapeutic use*
  • Patient Selection
  • Phenotype
  • Polymorphism, Genetic
  • Precision Medicine
  • Proline / analogs & derivatives
  • Sofosbuvir
  • Sulfonamides
  • Treatment Outcome
  • Uridine Monophosphate / adverse effects
  • Uridine Monophosphate / analogs & derivatives*
  • Uridine Monophosphate / therapeutic use

Substances

  • Antiviral Agents
  • Cyclopropanes
  • interferon-lambda, human
  • Interleukins
  • Lactams, Macrocyclic
  • Macrocyclic Compounds
  • Sulfonamides
  • Interferons
  • Proline
  • Uridine Monophosphate
  • paritaprevir
  • Sofosbuvir