Enhanced antiviral benefit of combination therapy with lamivudine and famciclovir against WHV replication in chronic WHV carrier woodchucks

Cell culture studies in our laboratory and others have previously demonstra ted synergistic antiviral activity for combinations of 3TC (lamivudine) and penciclovir against Hepatitis B Virus (HBV) replication and the Duck Hepat itis B Virus (DHBV). Based on these results, a study was designed to determ ine if an enhanced antiviral effect with combinations of 3TC and famciclovi r (FCV, oral prodrug of penciclovir) could be demonstrated in vivo using th e Woodchuck Hepatitis Virus (WHV)/woodchuck experimental model of chronic H BV infection. Both antiviral agents have been shown to be effective against WHV replication Fn WHV chronic carriers in previous studies by our laborat ories. The antiviral effects of four different combinations of lamivudine a nd FCV were found to be greater than those observed for the corresponding m onotherapies. All four combination treatments produced antiviral effects th at were at least equal to that expected for additive activity based on esti mations generated by Bliss Independence calculations. Two of the combinatio n treatments produced antiviral effects that were significantly greater tha n that expected for additive effects, indicative of synergistic antiviral i nteractions. These studies demonstrate that combination therapy of chronic WHV infection has enhanced antiviral benefit over corresponding monotherapi es and indicate that combination treatment of chronic HBV infection can be superior to therapies using a single antiviral agent. (C) 2000 Elsevier Sci ence B.V. All rights reserved.