The standard of care (SOC) therapy for patients with chronic hepatitis C virus (HCV) infection has been the use of both peginterferon (PegIFN) and ribavirin (RBV). These drugs are administered for either 48 weeks (HCV genotypes 1, 4, 5, and 6) or for 24 weeks (HCV genotypes 2 and 3), inducing sustained virologic response (SVR) rates of 40%-50% in those with
genotype 1 and of 80% or more in those with genotypes 2 and 3 infections.5-7 Once achieved, an SVR is associated with long-term clearance of HCV infection, http://www.selleckchem.com/products/ulixertinib-bvd-523-vrt752271.html which is regarded as a virologic “cure,” as well as with improved morbidity and mortality.8-10 Two major advances have occurred since the last update of treatment guidelines for chronic hepatitis C (CHC) that have changed the optimal treatment regimen of genotype 1 chronic Palbociclib chemical structure HCV infection: the development of direct-acting antiviral (DAA) agents11-17 and the identification of several single-nucleotide polymorphisms associated with spontaneous and treatment-induced clearance of HCV infection.18, 19 Although PegIFN and RBV remain vital components of therapy, the emergence of DAAs has led to a substantial improvement
in SVR rates and the option of abbreviated therapy in many patients with genotype 1 chronic HCV infection. A revision of the prior treatment guidelines is therefore necessary, but is based on data that are presently limited. Accordingly, there may be need to reconsider some of the recommendations as additional data become available. These guidelines review what treatment for genotype 1 chronic HCV infection is now regarded as optimal, but they do not address the issue of prioritization of patient selection for treatment or of treatment of special patient populations. There are multiple medchemexpress steps in the viral lifecycle that represent potential pharmacologic targets. A number of compounds encompassing at least five distinct drug classes are currently under development for the treatment of CHC. Presently, only inhibitors of the HCV nonstructural protein 3/4A (NS3/4A)
serine protease have been approved by the Food and Drug Administration (FDA). The NS3/4A serine protease is required for RNA replication and virion assembly. Two inhibitors of the NS3/4A serine protease, boceprevir (BOC) and telaprevir (TVR), have demonstrated potent inhibition of HCV genotype 1 replication and markedly improved SVR rates in treatment-naïve and treatment-experienced patients.12, 13, 16, 17 Limited phase 2 testing has shown that TVR also has activity against HCV genotype 2 infection but not against genotype 3.20 With regard to BOC, there are limited data indicating that it too, has activity against genotype 2 but also against genotype 3 HCV infection.21 However, at this time, neither drug should be used to treat patients with genotype 2 or 3 HCV infections, and when administered as monotherapy, each PI rapidly selects for resistance variants, leading to virological failure.