Abstract: The present invention relates generally to the field of Hepatitis B variants exhibiting a reduced sensitivity to nucleoside analogues both in vivo and in vitro. More in particular, reverse transcriptase mutant rt I233V is provided. Present invention provides assays and methods for detecting such variant, which assays are useful in monitoring anti-viral therapeutic regimes and adjusting patient therapy. A diagnostic kit for detecting the presence of an HBV variant in a biological sample has also been described. Finally, the use of a pharmaceutical composition to cure a subject suffering from a HBV infection, which HBV is resistant to lamuvidine and/or adefovir has been provided, which pharmaceutical composition comprises the nucleoside analogue tenofovir.