Combination therapy with lamivudine and famciclovir for chronic hepatitis B-infected Chinese patients: A viral dynamics study

In vitro studies have shown that lamivudine and penciclovir (the active met abolite of famciclovir) act synergistically to inhibit hepatitis B virus (H BV) replication. We compared the effectiveness of HBV viral suppression by lamivudine monotherapy versus lamivudine plus famciclovir combination thera py in Chinese patients with chronic HBV infection. Twenty-one Chinese hepat itis B e antigen (HBeAg)-positive patients, with detectable HBV DNA (Digene Hybrid Capture II), were randomized to receive either lamivudine 150 mg/d orally (group 1, 9 patients) or lamivudine 150 mg/d plus famciclovir 500 mg 3 times a day orally (group 2, 12 patients) for 12 weeks, with a follow-up period of at least 16 weeks. Serial serum HBV-DNA levels were determined a nd a mathematical model with provision for incomplete inhibition of virus p roduction during therapy was applied to analyze the dynamics of viral clear ance. The mean antiviral efficacy was significantly greater in group 2 than in group 1 (0.988 +/- 0.012 vs. 0.94 +/- 0.03, P = .0012). HBV DNA returne d to pretreatment level within 16 weeks after the end of initial treatment in 4 patients (66.7%) in group 1 and none in group 2 (P = .08), who remaine d HBeAg positive and received no further treatment after week 12. Hence, in Chinese chronic HBeAg-positive patients, combination therapy using lamivud ine and famciclovir was superior to lamivudine monotherapy in inhibiting HB V replication. Further studies of longer duration are needed to define whet her combination therapy will increase the HBeAg seroconversion rate and dec rease the rate of emergence of lamivudine-resistant variants.