Emergence of mutant hepatitis B virus during long-term lamivudine therapy in human immunodeficiency virus co-infected-patient

Seven patients co-infected with hepatitis B virus (HBsAg and HBeAg carriers , quantifiable HBV DNA with the bDNA technic) and human immunodefiency viru s received a triple antiretroviral combination therapy, including lamivudin e (150mg twice a day). Hepatitis B viral load rapidly became undetectable i n 6/7 patients. It remained below the level of detection in 2 subjects, aft er 20 and 22 months of treatment, with one of them achieving HBeAg/anti-HBe seroconversion. However, in the other 4 individuals, hepatitis B viremia i ncreased again after 8 to 16 months of lamivudine-containing regimen. The l ast patient was a non-responder. The 4 relapsers developed double mutation Leu(528) for Met(528) and Met(552) for Val(552), on hepatitis B virus polym erase, either concomitant (M8 and M16) with a hepatitis B virus DNA increas e, or 2 months earlier (M10 and M12). The high frequency of hepatitis B vir us resistance to lamivudine emphasizes the necessity of identifying more ef fective strategies, such as double combination therapies.