title: Sofosbuvir and ABT-450: terminator of hepatitis C virus?
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.
authors.affiliation: The Institute of Translational Hepatology, Beijing 302 Hospital, Peking University, Beijing 100039, China.
authors.forename: Qing-Lei
authors.initials: QL
authors.lastname: Zeng
authors.forename: Ji-Yuan
authors.initials: JY
authors.lastname: Zhang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Li-Feng
authors.initials: LF
authors.lastname: Wang
authors.forename: Fu-Sheng
authors.initials: FS
authors.lastname: Wang
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003521:Cyclopropanes; D004359:Drug Therapy, Combination; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D006518:Hepatitis Viruses / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D018579:Patient Selection; D010641:Phenotype; D011110:Polymorphism, Genetic; D057285:Precision Medicine; D011392:Proline / Q000031:analogs & derivatives; D000069474:Sofosbuvir; D013449:Sulfonamides; D016896:Treatment Outcome; D014542:Uridine Monophosphate / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D003521:Cyclopropanes; D007372:Interferons; D007378:Interleukins; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds; D011392:Proline; D000069474:Sofosbuvir; D013449:Sulfonamides; D014542:Uridine Monophosphate; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C585405:paritaprevir
keywords: ABT-450; Antiviral therapy; Hepatitis C virus; Sofosbuvir; Sustained virologic response