Tenofovir Disoproxil Fumarate for the Treatment of Lamivudine-Resistant Hepatitis B

Background & Aims: Lamivudine resistance occurs in patients with chronic hepatitis B at rates of 16%-32% after 1 year and 49% after 3years. Adefovir dipivoxil, a nucleotide analogue recently approved by the Food and Drug Administration for the treatment of chronic hepatitis B, is effective against hepatitis B virus (HBV) but has been associated with renal toxicity at high doses. Tenofovir disoproxil fumarate is another nucleotide analogue with demonstrated antiviral activity against both wildtype and lamivudine-resistant HBV. Tenofovir, at its licensed dose, has not been associated with renal dysfunction. Methods: We describe a series of 9 patients with lamivudine-resistant hepatitis B treated with tenofovir, 300 mg, once daily before the availability of adefovir. Levels of HBV DNA, alanine aminotransferase (ALT), hepatitis B e antigen (HBeAg), and antibody to HBeAg (anti-HBe) were monitored. Results: The addition of tenofovir to the existing regimen of lamivudine resulted in a median decline of 4.5 log(10) copies/mL in HBV DNA levels (range, 3.2-6.3 log(10) copies/mL) after a median treatment duration of 12 months (range, 6-16 mo). HBeAg seroconversion was observed in 2 patients, with a third patient undergoing HBeAg loss while remaining anti-HBe negative. In 4 of 7 patients with elevated ALT levels at baseline, ALT levels normalized. No significant adverse events were encountered during treatment. Conclusions: In patients with lamivudine-resistant hepatitis B, treatment with tenofovir is well tolerated and results in significant virological, serological, and biochemical improvements on par with those seen with high-dose adefovir (30 mg/day) therapy, without the complication of renal toxicity.