Multiple-drug-resistant mutants of feline immunodeficiency virus selected with 2',3'-dideoxyinosine alone and in combination with 3'-azido-3'-deoxythymidine.

Mutants of feline immunodeficiency virus (FIV) were selected in cell culture in the continuous presence of 10 microM (each) 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxyinosine (ddI). These mutants (AIR-1 and AIR-3) displayed a 13-fold resistance to AZT but had less than a 2-fold decrease in susceptibility to ddI. Interestingly, the AIR mutants were cross-resistant to phosphonoformate (PFA) and were hypersensitive to 2',3'-dideoxycytidine (ddC). Mutants of FIV were also selected in the presence of 10 microM ddI alone (DIS-1, DIS-2c), and these displayed a two- to fourfold decrease in susceptibility to ddI. Like the mutants selected with the combination of AZT plus ddI, DIS-1 and DIS-2c were cross-resistant to PFA and were hypersensitive to ddC. However, they remained as susceptible as wild-type FIV to AZT. Thus, the mutants selected with the combination of AZT plus ddI have phenotypes which reflect those obtained by selection with these drugs individually.