Adefovir dipivoxil for the treatment of lamivudine-resistant hepatitis B mutants

Lamivudine has been shown to be an effective therapy for chronic hepatitis B, but resistance to this nucleoside agent is common after prolonged use. F ive patients with chronic hepatitis B virus (HBV) infection developed resis tance to lamivudine after 9 to 19 months of treatment. In 4 patients this o ccurred after liver transplantation and the remaining individual had stable cirrhosis. In each case, resistance was confirmed to be caused by one or m ore mutations in the HBV-DNA polymerase gene and was associated with active underlying liver disease. The patients were treated with adefovir dipivoxi l in a dose of 5 to 30 mg daily. Two to 4 log(10) reductions in HBV-DNA lev els were observed in 4 cases, and the fifth patient became negative by quan titative polymerase chain reaction (PCR) after retransplantation in conjunc tion with hepatitis B immunoglobulin (HBIg). Virologic improvement was asso ciated with stable or declining serum alanine transaminase levels in 4 pati ents. HBV-DNA suppression has been sustained during a mean treatment period of 13 months (range 11 to 15 months), including I patient in whom lamivudi ne has been discontinued. Mild changes in renal function were observed duri ng treatment in most cases but did not require early discontinuation of the drug. This study provides evidence that adefovir dipivoxil can be an effec tive treatment for lamivudine-resistant HBV mutants as well as Wild-type HB V.