HCV resistance to drugs: still a scourge?

Francesca Ceccherini-Silberstein – Department of Experimental Medicine and Surgery, University Tor Vergata, – Rome, Italia


The goal of therapy is to cure hepatitis C virus (HCV) infection and preventing hepatic cirrhosis,
hepatocarcinoma, severe extrahepatic manifestations and death.
The identification and characterization of HCV encoded proteins and their functional units
contributed to the development of highly effective direct acting antivirals (DAA) against
the NS3 protease, NS5A and the NS5B polymerase. In these last years, the introduction of
the DAAs in clinical practice has revolutionized the HCV treatment, allowing to achieve
>90-95% rates of sustained virological response (SVR) in many groups of patients.
Despite the excellent efficacy of DAA containing regimens, virological failures can occur,
often associated with development of resistance and with differences according to the type
of regimen and HCV genotype. The natural presence of resistance associated substitutions
(RASs), as well as their rapid emergence during incomplete drug pressure, are intrinsic
characteristics of HCV that greatly affect treatment outcome and the chances to achieve
a virolgical cure.
Nowadays, a high number of RASs in NS3, NS5A, and NS5B have been associated in vivo
and/or in vitro with reduced susceptibility to DAAs. Understanding more about RASs may
help us learn why the patients failed, and may allow the optimization of both first-line
treatment for other new patients that should start treatment and also retreatment choices
for patients that already have failed a DAA containing regimen.
keywords: HCV; Hepatitis C virus; Genotype; Resistance associated substitutions; Direct acting antiviral agents; Genotypic resistance testing; Antiviral therapy

Articolo presente in – Cure and Chronicity N.1 

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