engleski

Molecular and clinical bases of anti-HCV drug resistance

With excellent efficacy of direct-acting antivirals (DAA) now available, treatment failure is rare, however, when it occurs, it is mostly due to relapse. On treatment failure is very rare. Baseline resistance-associated amino acid (aa) substitutions (RASs) are common, but do not frequently result in treatment failure. Therefore, detection of baseline mutations is not generally predictive of response. In addition, the frequency of resistant mutation data is often underestimated because virus <500 IU/ml cannot be deep sequenced, and therefore, is not included in resistance data. Mutations resulting in resistance have been identified, and involve NS5A and protease inhibitors. Resistance to NS5B polymerase inhibitors is rare. To minimize the development of resistance mutations, it is recommended to limit exposure to reliable compliant patients because missed doses increase the risk of development of resistance mutations. Use of multiple agent combinations with different mechanisms of action including NS5B inhibitors, increases the barriers to resistance and reduce the risk of development of resistance. In recently published real-life studies on DAA failures, RASs prevalence was remarkably high. These findings advocate for HCV resistance testing at failure, in order to optimize the second-line therapeutic options and to overcome treatment failure.

direct-acting antivirals ; treatment failure ; HCV resistance testing

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