Lamivudine and Adefovir to Treat Chronic Hepatitis B Infection in People With and Without HIV Infection

This clinical trial examines the addition of adefovir dipivoxil to a lamivudine regimen for treating chronic hepatitis B infection. Two patient populations will be separately recruited: HIV-infected (40 subjects) and HIV-uninfected (20 subjects). HIV-infected patients will be enrolled in a randomized, placebo controlled study of the safety and efficacy of the addition of adefovir to lamivudine for the treatment of chronic hepatitis B in subjects with a hepatitis B virus (HBV) viral load of at least one million copies/mL despite at least one year of lamivudine therapy. A similar population of HIV-uninfected subjects will be treated with open-label adefovir 10 mg daily for one year. These HIV-negative subjects will serve as a control group for immunological comparisons to the HIV-positive group treated with adefovir. HIV-infected subjects will be randomly allocated to receive adefovir 10 mg daily for one year or matching placebo. At the end of one year, HIV-infected patients may choose to receive open-label adefovir, and HIV-uninfected patients will have the option of continuing open-label drug if they are responding to treatment. Patients may not have decompensated cirrhosis or other causes of liver disease such as hepatitis C. Liver biopsies are performed prior to study and at the end of one year. HIV-positive subjects whose liver biopsy demonstrates cirrhosis will not be randomized but will be treated with open-label adefovir 10 mg daily. The purpose of the study is to evaluate the safety and efficacy of lamivudine plus adefovir as compared with continued lamivudine in HIV-infected patients, to compare responses between HIV-uninfected and HIV-infected subjects, and to obtain specimens for studies of immune responses to HBV. HIV-infected patients will receive lamivudine 150 mg bid plus adefovir 10 mg qd (or placebo) and HIV-uninfected subjects will receive lamivudine 100 mg qd plus adefovir 10 mg qd. L-carnitine supplementation will be used only if low serum carnitine levels are documented. Additionally, patients will have the option of enrolling in a sub-study assessing the kinetics of viral load response to study drug. Specimens will be stored for possible future determination of adefovir levels and use in evaluating HBV and HIV resistance to adefovir. Patients discontinuing study drug and not initiating a commerically available anti-HBV medication (including adefovir) will be monitored for safety for at least an additional 24 weeks. The primary study endpoint will be a comparison of the absolute HBV viral load at Week 48 between the placebo and adefovir HIV-positive patient groups, and for the HIV-negative population, the comparison of absolute HBV viral at Week 48 versus baseline. Secondary endpoints include safety, liver pathology, and transaminase level. Adefovir will be discontinued for toxicity; there will be no dose reduction. A DSMB will oversee the trial for toxicity.