Safety and efficacy of adefovir dipivoxil in patients infected with lamivudine-resistant hepatitis B and HIV-1☆

Background/Aims

Adefovir dipivoxil (10mg once-daily) was added to antiretroviral therapy including lamivudine in 35 HIV/HBV co-infected patients.

Methods

Parameters evaluated included alanine aminotransferase (ALT), HBV DNA and serological markers, HIV-1 RNA, and CD4+ cell count.

Results

Twenty-nine patients (83%) completed 144 weeks. Serum HBV DNA declined from a baseline 9.76log10 copies/mL (median) to 4.68, 5.24, and 5.90log10 copies/mL at weeks 48, 96, and 144, respectively (P<0.0001 at all time points). Seven patients (25%) achieved HBV DNA<2.3log10 copies/mL. No adefovir-associated resistance mutations in HBV DNA polymerase or HIV-1 reverse transcriptase were detected. ALT declined from 81 IU/L (median) at baseline by −16.0, −44.5, and −46.0 IU/L at week 48, 96 and 144, respectively (P=<0.05, respectively), and normalized in 71% of patients (20 of 28) by week 144. Two patients developed antibodies against HB ‘e’ antigen by week 48. No serious adverse events related to adefovir dipivoxil occurred during the study, and HIV-1 RNA and CD4+ cell counts were stable.

Conclusions

Treatment with adefovir dipivoxil for 144 weeks was well tolerated and resulted in significant and sustained reductions in HBV DNA and ALT in HIV/HBV co-infected patients. Efficacy increased with treatment duration, with no loss of viral suppression.

Keywords: Adefovir dipivoxil, Chronic hepatitis B, Human immunodeficiency virus, Lamivudine-resistance, Clinical trial