Fatma Abdelaziz Amer
Zagazig University, Egypt
Title: Direct acting antivirals; are they truely the last nails in the coffin of HCV ??
Biography
Biography: Fatma Abdelaziz Amer
Abstract
Nearly, 170 million people worldwide are suffering from chronic HCV infection. The introduction of the direct acting antivirals (DAAs) for the treatment has revolutionized the management of this major health problem. In addition to the currently available DAAs agents, recent drugs in the anti-HCV pipeline have enhanced capacity, as well as improved tolerance and safety profiles. High rates of sustained virologic response (SVR) are produced by DAAs in clinical trials (90%- 95%); nevertheless, treatment failure in real-life cohorts sometimes occurs. Treatment failure may present with null- response, breakthrough, partial response or relapse. In a given host, HCV population is a heterogeneous mixture of closely related genomes composed of the wild type plus other strains present at lower frequencies (HCV quasipecies). Under selective pressure of exposure to DAAs certain genetic variants which are normally present before start of treatment, can proliferate and become the dominant variant leading to treatment failure. These resistance associated mutations depend on the class of DAAs used and also vary between HCV genotypes and subtypes.
Breakthrough mutations have already been reported for NS3/4A protease inhibitors (O80K, V36AM, T54A/S, R1556K/T, A156S/T, D168N), for NS5A inhibitors (M28, Q30, L31V, Y93H), and for NS5B inhibitors (S282T, V321l, L159F). Emerging mutants can be detected by genotypic assays; population sequencing, clonal analysis and ultradeep sequencing. Phenotypic assays can also be used for the determination of drug susceptibility and cross-resistance profile / replicon system.
All efforts should be directed towards optimizing anti-HCV regimens to maximize SVR and minimize resistance.
