title: Forthcoming challenges in the management of direct-acting antiviral agents (DAAs) for hepatitis C.
abstract: 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 C(min)/IC(50) (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.
authors.affiliation: Department of Infectious Diseases, Foundation IRCCS San Matteo Hospital - University of Pavia, Pavia, Italy. raffaele.bruno@unipv.it
authors.forename: Raffaele
authors.initials: R
authors.lastname: Bruno
authors.forename: Serena
authors.initials: S
authors.lastname: Cima
authors.forename: Laura
authors.initials: L
authors.lastname: Maiocchi
authors.forename: Paolo
authors.initials: P
authors.lastname: Sacchi
mesh_terms: D000998:Antiviral Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D016174:Hepacivirus / Q000201:enzymology* / Q000235:genetics; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D015842:Serine Proteinase Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D015842:Serine Proteinase Inhibitors; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase