The present invention is directed to compounds, compositions and methods for treating or preventing viral infections, in particular, HIV, HBV, and HCV, in human patients or other animal hosts. The compounds are 3′-azido-2′,3′-dideoxy
purine nucleosides or phosphonates, and pharmaceutically acceptable, salts, prodrugs, and other derivatives thereof. In particular, the compounds show potent antiviral activity against HIV-1 resistance mutants including HIV-1K65R, HTV-1K70E, HIV-1L74V, HIV-1M184V, HIV-1Q151M and inhibitory activity against HIV-1 RT harboring TAMS or
insertion mutations including HIV-1AZT3, HIV-1AZT7, HIV-1AZT9, HIV-1Q151M, or HIV-169
insertion. In one embodiment, the compounds are 3′-azido-ddA, 3′-azido-ddG, or combinations thereof, administered with one or more additional antiviral agents that select for TAM mutations and / or the M 184V
mutation, along with a pharmaceutically acceptable carrier.