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

• Published in: Antiviral research 2000, Vol.45 (1), p.19-32
• Main Authors: Korba, Brent E, Cote, Paul, Hornbuckle, William, Schinazi, Raymond, Gerin, John L, Tennant, Bud C
• Format: Article
• Language: English
• Subjects: 2-Aminopurine - analogs & derivatives; 2-Aminopurine - therapeutic use; AIDS/HIV; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - therapeutic use; Biological and medical sciences; Carrier State; Combination antiviral therapy; combination therapy; Disease Models, Animal; Drug Therapy, Combination; Duck hepatitis B virus; Experimental animal model; Famciclovir; Hepatitis B Virus; Hepatitis B Virus, Woodchuck - drug effects; Hepatitis B, Chronic - drug therapy; Lamivudine; Lamivudine - therapeutic use; Marmota; Medical sciences; Pharmacology. Drug treatments; Prodrugs - therapeutic use; Reverse Transcriptase Inhibitors - therapeutic use; Viremia - drug therapy; Viremia - virology; Virus Replication - drug effects; Woodchuck Hepatitis Virus
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/S0166-3542(99)00072-8

Cell culture studies in our laboratory and others have previously demonstrated synergistic antiviral activity for combinations of 3TC (lamivudine) and penciclovir against Hepatitis B Virus (HBV) replication and the Duck Hepatitis B Virus (DHBV). Based on these results, a study was designed to determine if an enhanced antiviral effect with combinations of 3TC and famciclovir (FCV, oral prodrug of penciclovir) could be demonstrated in vivo using the Woodchuck Hepatitis Virus (WHV)/woodchuck experimental model of chronic HBV infection. Both antiviral agents have been shown to be effective against WHV replication in WHV chronic carriers in previous studies by our laboratories. The antiviral effects of four different combinations of lamivudine and FCV were found to be greater than those observed for the corresponding monotherapies. All four combination treatments produced antiviral effects that were at least equal to that expected for additive activity based on estimations generated by Bliss Independence calculations. Two of the combination treatments produced antiviral effects that were significantly greater than that expected for additive effects, indicative of synergistic antiviral interactions. These studies demonstrate that combination therapy of chronic WHV infection has enhanced antiviral benefit over corresponding monotherapies and indicate that combination treatment of chronic HBV infection can be superior to therapies using a single antiviral agent.