EXPERTISE : HCV Resistance

From viral resistance understanding to new molecules development


Expertise resistance : failure of current treatment in 44% of cases.

  • The need : drug resistance makes all existing anti HCV drugs obsolete.

  • Toxic side effects result in poor compliance and high treatment failure rates.
Consequently, it is a new drug.
HCV drug resistance : experience in the treatment of human immunodeficiency virus (HIV) and Hepatitis B Virus (HBV) infections with specific inhibitors of viral enzymes and cell entry shows that, apart from non adherence to therapy, the principal cause of treatment failure is viral resistance.

This concept is characterized by the selection of minor viral populations with mutation that confers resistance in the Huh7 cell replicon system.
Based on our knowledges in antiviral resistance, we described the mechanisms of the HCV protease inhibitors main resistance at a molecular level. The mutation is sufficient to confer a high level of resistance to HCV protease inhibitors.

The future main problem of HCV treatment is the phenomenon of drug resistance. As new HCV specific inhibitors enter clinical trials, resistance could become a major problem in patients treated with drug targeting HCV NS3-4A serine protease or NS5B RNA polymerase.
Mutations against 4 HCV protease inhibitors clinical were reported : BILN 2061, VX950, SCH6 and SCH503034. The in vitro resistance mutation selected against these inhibitors resulted in a significant to a drastic reduction in drug susceptibility.

These studies suggest that future Hepatitis C therapy involving small molecule inhibitors of HCV enzyme might require multi-drug combination like current HIV treatments. Currently, combination of HCV drugs represent an essential strategy to suppress the emergence of resistance by increasing the antiviral potency and efficiency.