• Proportion of subjects who achieve HBV DNA < the lower limit of quantitation (LLD LOQ) for the Roche COBAS® TaqMan -(LOQ = 29 IU/mL [approximately 169 copies/mL] [ Time Frame: HPS assay at Weeks 48 and 96 ] [ Designated as safety issue: No ]
• Proportion of subjects who achieve HBV DNA < the lower limit of detection (LOD) for the Roche COBAS® Taqman - (LOD = 10 IU/mL [approximately 58 copies/mL]) [ Time Frame: HPS assay at Weeks 48 and 96 ] [ Designated as safety issue: No ]
• Proportions of subjects with HBV DNA in clinically relevant categories (eg HBV DNA values categorized in ranges that differ by 10 log increments) [ Time Frame: at 48 weeks ] [ Designated as safety issue: No ]
• Proportion of subjects with ALT > 1 x upper limit of normal (ULN) at baseline who achieve ALT normalization (<= 1 x ULN) [ Time Frame: at Weeks 48 and 96 ] [ Designated as safety issue: No ]
• Descriptive rates of resistance in each treatment arm [ Time Frame: through Weeks 48 and 96 ] [ Designated as safety issue: No ]

• HBeAg loss at Weeks 48 and 96
• Virologic rebound due to genotypic resistance
• Frequency of adverse events, serious adverse events, and discontinuations from study drug due to adverse events or laboratory abnormalities
• To compare the proportion of subjects in the combination therapy group to the proportion of subjects in each of the monotherapy groups who achieve HBV DNA <50 IU/mL (approximately 300 copies/mL) at Week 96
• Mean Log10 reduction from baseline in HBV DNA at Weeks 48 and 96
• ALT normalization (≤ 1 x upper limit of normal) at Weeks 48 and 96
• HBe seroconversion at Weeks 48 and 96
• HBs seroconversion at Weeks 48 and 96

The purpose of this study is to evaluate the effectiveness of entecavir plus adefovir combination therapy versus entecavir monotherapy or therapy with adefovir plus lamivudine

• Drug: Entecavir
• Drug: Tenofovir
• Drug: Adefovir
• Drug: Lamivudine

Inclusion Criteria:

• Evidence of lamivudine resistance
• Subjects must have a history of previous lamivudine treatment at screening, and must have evidence of at least 1 LVD resistance substitution (valine, isoleucine, or serine) at reverse transcriptase codon 204 (M204V/I/S)
• Nucleoside- and nucleotide-naive, except for lamivudine
• Males or females ≥16 years of age (or minimum age of consent in a given country)
• Compensated liver function
• HBV DNA > 1.72 x 10*4* (approximately 10*5* copies/mL)
• Documentation of HBeAg-positive and HBeAb-negative status at screening
• Males and females >=16 years of age (or minimum age of consent in a given country)
• Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study (and for up to 6 weeks after the last dose of investigational product) in such a manner that the risk of pregnancy is minimized
• WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal. Post menopausal is defined as:
• Amenorrhea >= 12 consecutive months without another cause
• For women with irregular menstrual periods and on hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL
• Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where partner is sterile (e.g., vasectomy), should be considered to be of child bearing potential
• WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of investigational product

Exclusion Criteria:

• Evidence of decompensated cirrhosis
• Coinfection with HIV, HCV, or HDV
• Laboratory values out of protocol-specified range