Safety and efficacy of adefovir dipivoxil in patients co-infected with HIV-1 and lamivudine-resistant hepatitis B virus: an open-label pilot study

Background Lamivudine-resistant hepatitis B virus (HBV) is found in about 1 5-32% of infected patients with or without co-infection with HIV-1 after 1 year of lamivudine therapy. Adefovir dipivoxil is active in vivo and in vit ro against wild-type and lamivudine-resistant HBV. We assessed the safety a nd efficacy of a once daily dose of adefovir dipivoxil in an open-label tri al for the treatment of lamivudine-resistant HBV infection in HIV-1-infecte d patients. Methods 35 HIV-1/HBV co-infected patients receiving lamivudine therapy (150 mg twice daily) as part of their current HIV-1 antiretroviral regimen were enrolled. Patients received a 10 mg once-daily dose of adefovir dipivoxil for 48 weeks while maintaining their existing anti-HIV-1 therapy, including lamivudine. Patients were assessed every 4 weeks for safety and efficacy. Findings Four patients withdrew from the study (two because of adverse even ts), leaving 31 patients who received adefovir dipivoxil for a median of 48 weeks (range 44-48). Mean decreases in serum HBV DNA concentrations from b aseline (log 8.64 copies/mL [SE log 0.08]) were -log 3.40 copies/mL [log 0. 12] at week 24 (n=31) and -log 4.01 copies/mL [log 0.17] at week 48 (n=29; p<0.0001). Two patients underwent hepatitis B e antigen seroconversion-one at week 32 and one at week 36. Adefovir dipivoxil was generally well tolera ted, but was associated with a transient increase in serum alanine aminotra nsferase concentrations in 15 patients. We found no significant changes in either HIV-1 RNA or CD4 cell count. Interpretation These results indicate that 48 weeks of 10 mg daily adefovir dipivoxil is well tolerated and active against lamivudine-resistant HBV in HIV-1/HBV co-infected patients.