Dual sofosbuvir and ribavirin therapy for chronic hepatitis C infection

Sofosbuvir is the first pan-genotypic direct acting antiviral agent to be approved. This article provides an overview of the pharmacology of sofosbuvir and ribavirin and a comprehensive summary of the phase 2 and 3 studies supporting dual sofosbuvir and ribavirin therapy for chronic hepatitis C infection. With the production of generic formulations of sofosbuvir, we anticipate this regimen leading the first wave for widespread, IFN-free treatment and becoming first line for all genotypes (including genotype 1) for much of the world—in particular in developing and middle income countries. We discuss the continued challenges with this regimen including among patients with decompensated liver disease and post-liver transplant, and renal failure. We address concerns of emerging resistance. We also discuss the future prospects including the global uptake of sofosbuvir and ribavirin for the treatment of all genotypes.

[1]  H. Masur,et al.  Successful Retreatment of Chronic HCV Genotype-1 Infection With Ledipasvir and Sofosbuvir After Initial Short Course Therapy With Direct-Acting Antiviral Regimens. , 2016, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[2]  M. Yuen,et al.  Sofosbuvir plus ribavirin for the treatment of patients with chronic genotype 1 or 6 hepatitis C virus infection in Hong Kong , 2016, Alimentary pharmacology & therapeutics.

[3]  E. Barnes,et al.  Efficacy of sofosbuvir plus ribavirin with or without peginterferon-alfa in patients with hepatitis C virus genotype 3 infection and treatment-experienced patients with cirrhosis and hepatitis C virus genotype 2 infection. , 2015, Gastroenterology.

[4]  P. Belperio,et al.  Effectiveness of sofosbuvir‐based regimens in genotype 1 and 2 hepatitis C virus infection in 4026 U.S. Veterans , 2015, Alimentary pharmacology & therapeutics.

[5]  S. Saab,et al.  Treating fibrosing cholestatic hepatitis C with sofosbuvir and ribavirin: a matched analysis , 2015, Clinical transplantation.

[6]  G. Shiha,et al.  Sofosbuvir plus ribavirin for treating Egyptian patients with hepatitis C genotype 4. , 2015, Journal of hepatology.

[7]  J. McHutchison,et al.  Serum and cellular ribavirin pharmacokinetic and concentration-effect analysis in HCV patients receiving sofosbuvir plus ribavirin. , 2015, The Journal of antimicrobial chemotherapy.

[8]  S. Lim,et al.  A 2015 roadmap for the management of hepatitis C virus infections in Asia , 2015, The Korean journal of internal medicine.

[9]  J. Murray,et al.  Ribavirin Reduces Absolute Lymphocyte Counts in Hepatitis C Virus-Infected Patients Treated With Interferon-Free, Direct-Acting Antiviral Regimens. , 2015, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[10]  G. Cooke,et al.  Long-Term Treatment Outcomes of Patients Infected With Hepatitis C Virus: A Systematic Review and Meta-analysis of the Survival Benefit of Achieving a Sustained Virological Response , 2015, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[11]  R. Fontana,et al.  Sofosbuvir compassionate use program for patients with severe recurrent hepatitis C after liver transplantation , 2015, Hepatology.

[12]  S. Mikhail,et al.  Sofosbuvir plus ribavirin for the treatment of chronic genotype 4 hepatitis C virus infection in patients of Egyptian ancestry. , 2015, Journal of hepatology.

[13]  R. Chung,et al.  LP08 : Safety and efficacy of sofosbuvir-containing regimens in hepatitis C infected patients with reduced renal function: Real-world experience from HCV-target , 2015 .

[14]  H. Masur,et al.  LP09 : High efficacy of retreatment with ledipasvir and sofosbuvir in HCV patients who failed initial short course therapy with combination DAA regimens (nih synergy trial) , 2015 .

[15]  J. Kao,et al.  P0809 : 98% SVR12 in Korean And Taiwanese patients with chronic genotype 2 HCV infection receiving 12 weeks of sofosbuvir plus ribavirin: Results from an international, multicenter phase 3 study , 2015 .

[16]  M. Manns,et al.  O007 : All oral HCV therapy is safe and effective in patients with decompensated cirrhosis: Interim report from the HCV-target real world experience , 2015 .

[17]  J. Rockstroh,et al.  Sofosbuvir plus ribavirin for treatment of hepatitis C virus in patients co-infected with HIV (PHOTON-2): a multicentre, open-label, non-randomised, phase 3 study , 2015, The Lancet.

[18]  S. Kottilil,et al.  Sofosbuvir for treatment of chronic hepatitis C , 2015, Hepatology International.

[19]  N. Parkin,et al.  Infrequent development of resistance in genotype 1-6 hepatitis C virus-infected subjects treated with sofosbuvir in phase 2 and 3 clinical trials. , 2014, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[20]  H. Razavi,et al.  Global epidemiology and genotype distribution of the hepatitis C virus infection. , 2014, Journal of hepatology.

[21]  T. Ide,et al.  Sofosbuvir plus ribavirin in Japanese patients with chronic genotype 2 HCV infection: an open‐label, phase 3 trial , 2014, Journal of viral hepatitis.

[22]  K. Mounzer,et al.  Sofosbuvir and ribavirin for hepatitis C in patients with HIV coinfection. , 2014, JAMA.

[23]  Riina Salupere,et al.  Sofosbuvir and ribavirin in HCV genotypes 2 and 3. , 2014, The New England journal of medicine.

[24]  Sanjeev Arora,et al.  Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. , 2014, The New England journal of medicine.

[25]  Brad J. Wood,et al.  Sofosbuvir and ribavirin for hepatitis C genotype 1 in patients with unfavorable treatment characteristics: a randomized clinical trial. , 2013, JAMA.

[26]  E. Schiff,et al.  Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. , 2013, The New England journal of medicine.

[27]  John McNally,et al.  Sofosbuvir for previously untreated chronic hepatitis C infection. , 2013, The New England journal of medicine.

[28]  C. Stedman,et al.  Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C. , 2013, The New England journal of medicine.

[29]  M. Manns,et al.  Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. , 2012, JAMA.

[30]  Bernadette A. Thomas,et al.  Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010 , 2012, The Lancet.

[31]  M. Otto,et al.  Genotype and Subtype Profiling of PSI-7977 as a Nucleotide Inhibitor of Hepatitis C Virus , 2012, Antimicrobial Agents and Chemotherapy.

[32]  A. Wolkoff,et al.  Effectiveness of hepatitis C treatment with pegylated interferon and ribavirin in urban minority patients , 2010, Hepatology.

[33]  Christopher JL Murray,et al.  Health metrics and evaluation: strengthening the science , 2008, The Lancet.

[34]  M. Manns,et al.  Sustained Virologic Response and Clinical Outcomes in Patients with Chronic Hepatitis C and Advanced Fibrosis , 2007, Annals of Internal Medicine.

[35]  M. Alter,et al.  The Prevalence of Hepatitis C Virus Infection in the United States, 1999 through 2002 , 2006, Annals of Internal Medicine.

[36]  M. Thod Global Burden of Disease (GBD) for Hepatitis C , 2004, Journal of clinical pharmacology.

[37]  W. Kim,et al.  The burden of hepatitis C in the United States , 2002, Hepatology.

[38]  Z. Hong,et al.  Mechanism of action of ribavirin in the combination treatment of chronic HCV infection , 2002, Hepatology.

[39]  J. Berlin,et al.  The association between hepatitis C infection and survival after orthotopic liver transplantation. , 2002, Gastroenterology.

[40]  X. Forns,et al.  Hepatitis C virus kinetics during and immediately after liver transplantation , 2002, Hepatology.

[41]  J. Mir,et al.  Natural history of clinically compensated hepatitis C virus–related graft cirrhosis after liver transplantation , 2000, Hepatology.

[42]  E L Murphy,et al.  Prevalence of hepatitis C virus infection in the United States. , 1999, The New England journal of medicine.

[43]  Inda,et al.  The prevalence of hepatitis C virus infection in the United States, 1988 through 1994. , 1999, The New England journal of medicine.

[44]  M. Manns,et al.  Sofosbuvir and ribavirin for treatment of compensated recurrent hepatitis C virus infection after liver transplantation. , 2015, Gastroenterology.

[45]  E. Schiff,et al.  Sofosbuvir and ribavirin prevent recurrence of HCV infection after liver transplantation: an open-label study. , 2015, Gastroenterology.

[46]  J. Pawlotsky,et al.  EASL Recommendations on Treatment of Hepatitis C 2015. , 2015, Journal of hepatology.

[47]  D. Harnois,et al.  Aging of Hepatitis C Virus (HCV)-Infected Persons in the United States: A Multiple Cohort Model of HCV Prevalence and Disease Progression , 2010 .

[48]  Mary Ellen Kitler,et al.  Global burden of disease (GBD) for hepatitis C , 2004 .

[49]  Alan D. Lopez,et al.  The Global Burden of Disease Study , 2003 .

[50]  J. Emparanza,et al.  [The prevalence of hepatitis C virus infection]. , 1998, Gastroenterologia y hepatologia.

[51]  J. Connor,et al.  The metabolism of ribavirin in erythrocytes and nucleated cells. , 1990, The International journal of biochemistry.