tenofovir disoproxil fumarate (tenofovir df) versus emtricitabine/tenofovir df in subjects resistant to lamivudine

Conditions: Hepatitis B

Summary: the aim of therapy for the treatment of chronic hepatitis b virus (hbv) is to maintain suppression of viral replication to prevent the emergence of complications, which requires long-term therapy. durable suppression of viral replication is achieved in the treatment of chronic viral diseases by preventing of the emergence of drug-resistant mutations. the clinical guidelines for the management of lamivudine resistant patients are variable. some recommend switching to another agent without cross-resistance, while others recommend adding on another agent without cross-resistance. limited clinical data exists to demonstrate whether tenofovir disoproxil fumarate (tenofovir df; tdf) is an effective monotherapy for lamivudine resistant patients or if it should be used as part of a combination therapy regimen. this study is designed to evaluate the effectiveness, safety, and tolerability of tenofovir df monotherapy versus emtricitabine (ftc)/tenofovir df combination therapy in participants with chronic hbv with lamivudine resistance (presence of the rtm204i/v mutation with or without the rtl180m mutation) over a 240-week period. participants in this study must be receiving lamivudine treatment at the time of enrollment.


Eligibility criteria:
inclusion criteria * chronic hbv infection, defined as positive serum hbsag for at least 6 months * 18 through 75 years of age, inclusive * hbv dna ≥ 10\^3 iu/ml * receiving treatment with lamivudine with confirmation of hbv reverse transcriptase mutation(s) known to confer resistance to lamivudine (rtm204i/v with or without rtl180m) by central laboratory assessment prior to randomization; adefovir dipivoxil treatment of ≤ 48 weeks at the time of screening (inclusive of combination adefovir dipivoxil + lamivudine at entry) was allowed * willing and able to provide written informed consent * negative serum pregnancy test (for females of childbearing potential only) * calculated creatinine clearance ≥ 50 ml/min * hemoglobin ≥ 10 g/dl * neutrophils ≥ 1000 /mm\^3 * no prior oral hbv therapy with approved nucleotide and/or nucleoside therapy or other investigational agents for hbv infection other than lamivudine or adefovir dipivoxil exclusion criteria * pregnant women, women who are breast feeding or who believe they may wish to become pregnant during the course of the study * males and females of reproductive potential who are not willing to use an effective method of contraception during the study * alanine aminotransferase (alt) ≥ 10 × the upper limit of the normal range (uln) * decompensated liver disease * interferon or pegylated interferon therapy within 6 months of the screening visit * alpha fetoprotein \> 50 ng/ml * evidence of hepatocellular carcinoma * coinfection with hepatitis c virus, hiv, or hepatitis d virus * significant renal, cardiovascular, pulmonary, or neurological disease * received solid organ or bone marrow transplantation * receiving therapy with immunomodulators (eg, corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents susceptible of modifying renal excretion * proximal tubulopathy * known hypersensitivity to the study drugs, the metabolites or formulation excipients

Keywords: tenofovir df emtricitabine chronic hepatitis b combination therapy