Safety and efficacy of adefovir dipivoxil in patients co-infected with HIV-1 and lamivudine-resistant hepatitis B virus: an open-label pilot study [Benhamou Y, et al. Lancet 2001:358:718] This is an open-label study of 35 patients with HIV-1 and HBV co-infection who were receiving lamivudine for HIV therapy. Treatment of HBV consisted of adefovir, 10 mg daily for 48 weeks. The results showed a mean decrease in serum HBV DNA concentrations of 4.0 log₁₀ C/mL at week 48. There was no significant change in HIV RNA plasma levels or CD4 cell counts. The authors conclude that adefovir is well tolerated and highly active in treating lamivudine-resistant HBV in HIV co-infected patients.
Comment: A prior phase two controlled clinical trial of adefovir for HBV used doses of 5, 30, and 60 mg adefovir daily for 12 weeks; the 30 mg dose was highly effective, but caused nephrotoxicity, and the 5 mg/day dose showed less anti-HBV activity. These observations led to the dose selection in the trial presented. The authors point out that lamivudine inhibits HBV replication in over 80% of patients, but resistance develops in 15-32% of immunocompetent patients at one year, and this rate is significantly higher with longer courses of treatment and with HIV co-infection. Adefovir is active against wild-type, lamivudine-resistant, and famciclovir-resistant strains of HBV. This drug was used previously for antiretroviral treatment in doses of 60 and 120 mg/day, but activity was marginal and nephrotoxicity was a major problem so this became the first drug rejected by the FDA for HIV infection. The dose used here, 10 mg/day, was well tolerated. Nevertheless, the authors urge care when adefovir is co-administered with other potentially nephrotoxic drugs even at this low dose.
posted 9/25/2001

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