Forthcoming challenges in the management of direct-acting antiviral agents (DAAs) for hepatitis C

Raffaele Bruno, Serena Cima, Laura Maiocchi, Paolo Sacchi

Research output: Contribution to journalArticlepeer-review


Agents that specifically target the replication cycle of the virus direct-acting antiviral agents (DAAs) by directly inhibiting the NS3/4A serine protease, the NS5B polymerase and NS5A are currently in clinical development. The need to achieve serum drug concentrations able to suppress viral replication is a key factor for a successful antiviral therapy and the prevention of resistance. Thus pharmacokinetics parameters became important issues for drugs used in the therapy of hepatitis C. The ratio of Cmin/IC50 (inhibitory quotient or IQ) can provide a surrogate measure of a drug's ability to suppress HCV replication, by taking into account the relationship between plasma drug levels and viral susceptibility to the drug. Ritonavir boosting may be a useful strategy to improve pharmacokinetic parameters. Characterising resistance to DAAs in clinical trials is essential for the management of a drug regimen to reduce the development of resistance and thereby maximise SVR rate. The lesson of HIV therapy, provide a compelling case for the exploration of combinations of direct-acting antiviral agents.

Original languageEnglish
Pages (from-to)337-344
Number of pages8
JournalDigestive and Liver Disease
Issue number5
Publication statusPublished - May 2011


  • DAA
  • Pharmacokinetics
  • Resistance
  • Ritonavir boosting

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology


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