1.Non-interferon Therapies for Hepatitis C    Current Hepatitis Reports    2012
Abstract:Hepatitis C (HCV) therapy is currently undergoing a revolution with the development of new classes of Direct Acting Antivirals (DAAs) with distinct mechanisms of action, potency, resistance patterns and significantly less side effects compared to current standard of care therapies. Our patients have struggled with interferon based therapies for the last 2 decades, but now we are at a turning point with the development of new non-interferon combinations of DAAs. These new molecules have demonstrated to be effective, safe and most importantly have shown the capacity to achieve a sustained virological response in the absence of interferon. This article summarizes the available published clinical trials that are rapidly contributing to our understanding of how we might need to combine these new antivirals to achieve the highest rates of cure in HCV patients who are treatment naïve, non-responders or cirrhotic, across all genotypes.
2.Naturally occurring resistance mutations to inhibitors of HCV NS5A region and NS5B polymerase in DAA treatment-naïve patients    Virology Journal    2013
Abstract:
Background
Direct-acting antiviral (DAA) agents target HCV proteins; some of these have already been approved for the treatment of HCV infection, while others are in development. However, selection of DAA-resistant viral variants may hamper treatment. The aim of this study was to illustrate potential natural DAA-resistance mutations in the HCV NS5A and NS5B regions of HCV genotypes 1a and 1b from DAA-naïve patients.
Methods
Direct sequencing of HCV NS5A and NS5B regions was performed in 32 patients infected with HCV genotype 1a and 30 patients infected with HCV genotype 1b; all subjects were naïve to DAAs.
Results
In genotype 1a strains, resistance mutations in NS5A (M28V, L31M and H58P) were observed in 4/32 (12.5%) patients, and resistance mutations in NS5B (V321I, M426L, Y448H, Y452H) were observed in 4/32 (12.5%) patients. In genotype 1b, resistance mutations in NS5A (L28V, L31M, Q54H, Y93H and I280V) were observed in 16/30 (53.3%) patients, while resistance mutations in NS5B (L159F, V321I, C316N, M426L, Y452H, R465G and V499A) were observed in 27/30 (90%) patients.
Conclusions
Mutations conferring DAA resistance were detected in NS5A and NS5B of HCV genotypes 1a and 1b from DAA-naïve patients. Although some mutations confer only a low level of resistance, the presence at baseline of mutated HCV variants should be taken into consideration in the context of DAA therapy.