Korba B E, Cote P, Hornbuckle W, Schinazi R, Gerin J L, Tennant B C
Division of Molecular Virology and Immunology, Georgetown University Medical Center, Rockville, MD, USA.
Antiviral Res. 2000 Jan;45(1):19-32. 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.
我们实验室及其他机构之前进行的细胞培养研究已证明，3TC（拉米夫定）与喷昔洛韦联合使用对乙型肝炎病毒（HBV）复制及鸭乙型肝炎病毒（DHBV）具有协同抗病毒活性。基于这些结果，设计了一项研究，以确定在土拨鼠肝炎病毒（WHV）/土拨鼠慢性HBV感染实验模型中，3TC与泛昔洛韦（FCV，喷昔洛韦的口服前体药物）联合使用是否能在体内显示出增强的抗病毒效果。在我们实验室之前的研究中，这两种抗病毒药物已被证明对WHV慢性携带者的WHV复制有效。结果发现，拉米夫定与FCV的四种不同联合用药的抗病毒效果均大于相应单一疗法。所有四种联合治疗产生的抗病毒效果至少与基于布利斯独立性计算得出的相加活性预期效果相当。其中两种联合治疗产生的抗病毒效果显著大于相加效应预期效果，表明存在协同抗病毒相互作用。这些研究表明，慢性WHV感染的联合治疗比相应的单一疗法具有更强的抗病毒益处，也表明慢性HBV感染的联合治疗可能优于单一抗病毒药物治疗。
