• To compare the antiviral efficacy against HBV of once-daily tenofovir DF versus once-daily emtricitabine plus tenofovir DF combination treatment in subjects with lamivudine resistance [ Time Frame: After last subjects completes 48 weeks of blinded treatment ] [ Designated as safety issue: No ]
  

• To evaluate the safety and tolerability of tenofovir DF versus emtricitabine plus tenofovir DF combination treatment in subjects with lamivudine resistance [ Time Frame: Throughout the 240 week study duration ] [ Designated as safety issue: Yes ]
  

The aim of therapy for the treatment of chronic hepatitis B is to maintain suppression of the viral replication to prevent the emergence of complications. Achieving this goal requires long-term therapy. Chronically administered treatments for any disease should have the following properties to be suitable: long-term tolerability, practicality (linked with adherence), potency, and durability of effect. Durable suppression of viral replication is achieved in the treatment of chronic viral diseases through the prevention of emergence of drug-resistance mutations; to this end, monotherapies have been found to be insufficient in most chronic viral diseases. In the setting of chronic hepatitis B, the use of combination therapy (when the combined drugs have different resistance profiles) is likely to reduce the rate of development of drug resistance mutations.

Therefore, the use of combination therapy for the treatment of chronic hepatitis B represents a potential advance in the treatment of this disease where monotherapies may have limitations.

Accordingly, the present study will compare the efficacy and safety of tenofovir DF to emtricitabine plus tenofovir DF in chronic hepatitis B subjects currently receiving lamivudine monotherapy with lamivudine associated resistance mutations (rtM204V/I with or with the rtL180M). In addition, the study will help to further elucidate the PK profiles of tenofovir DF in patients with mild (CLcr 50-80 mL/min) renal impairment to provide better guidance for the use of this drug in this patient population.

This is a randomized, double-blind, double-dummy, 240-week study comparing the antiviral efficacy, safety, and tolerability of tenofovir DF versus the fixed-dose combination of emtricitabine/tenofovir DF for the treatment of chronic HBV infection. Enrolled subjects must be currently receiving lamivudine and must be deemed lamivudine resistant (confirmed lamivudine resistance-associated mutation[s] in the HBV polymerase gene and an HBV deoxyribonucleic acid [DNA] level of >/= 4 log10 copies/mL at screening). Adefovir dipivoxil treatment of </= 48 weeks inclusive of combination adefovir dipivoxil + lamivudine treatment at entry is allowed.

Approximately 250 subjects will be randomized in a 1:1 ratio to treatment arm A or B.

Treatment Arm A: tenofovir DF 300 mg once daily plus emtricitabine/tenofovir DF placebo once daily

Treatment Arm B: emtricitabine 200 mg/tenofovir DF 300 mg once daily plus tenofovir DF placebo once daily

Randomization will be stratified by hepatitis e antigen (HBeAg) status (negative or positive) and alanine aminotransferase (ALT) level (>/= 2 × upper limit of normal [ULN] or < 2 × ULN) at screening.