The good, the bad and the ugly of the new treatments for hepatitis C virus.

analysis of sofosbuvir/ribavirin versus sofosbuvir/ simeprevir for genotype 1 hepatitis C virus in inter-feron-ineligible/intolerant individuals. Approximately 185 million people worldwide have chronic hepatitis C virus (HCV) infection, and more than 350,000 people die of HCV-related liver diseases each year. Until 2011, the standard of care for patients with HCV genotype1 (GT1) was pegylated interferon (PEG-IFN) plus ribavirin, which in clinical trials have shown a moderate efficacy unfortunately with many adverse effects. The sustained virologic response (SVR) rates were 40 to 50%. 1,2 At that time, first-in-class protease inhibitors [(PIs) (boceprevir and telaprevir)] were the first direct-acting antiviral (DAA) therapies approved for patients with GT1, given in conjunction with both PEG-IFN and ribavirin for a total of 24 to 48 weeks, depending on whether the patient had a robust response (ranged from 63 to 75%). 3,4 Fortunately, with the development of the second wave of DAA which are specifically designed to target HCV proteins, particularly the non-structural proteins, there are new therapies available. In fact, the efforts have fo-cused on the six nonstructural (NS) proteins (NS2, NS3, NS4A, NS4B, NS5A, and NS5B) that play critical roles in HCV entry, replication, and proliferation and will serve as possible targets for the development more DAA therapies. The good of the DAA is that they can reduce the length of antiviral treatment, improve response rates, and allow for interferon-free regimens for some HCV genotypes. On the other hand, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) offers two options for interferon (IFN)-neligible/intolerant individuals with GT1 infection: sofosbuvir/ribavirin (SOF/RBV) for 24 weeks or sofosbuvir/simeprevir (SOF/SMV) for 12 weeks. A 24-week course of SOF/ RBV costs approximately US$169,000, with SVR rates ranging from 52% to 84%; 12 weeks of SOF/ SMV costs approximately $150,000, with SVR between 89% and 100%. Hogan, et al. 5 have analyzed the cost effectiveness of these two treatment regimens accounting for costs of drugs, treatment-related medical care, re-treatment for individuals who do not achieve SVR, and natural history of continued HCV infection after failed retreatment. Those investigators found that SOF/SMV yielded lower costs and more quality-adjusted life years (QALYs) for the average subject, compared to SOF/RBV ($165,336 and 14.69 QALYs vs. $243,586 and 14.45 QALYs, respectively). In base-case cost analysis, the SOF/SMV treatment strategy saved $91,590 per SVR, compared to SOF/ RBV. The results of this study suggest that the combination …