Mutations in the human immunodeficiency virus type 1 reverse transcriptasegene observed in stavudine and didanosine strains obtained by in vitro passages

We have selected a human immunodeficiency virus type 1 (HIV1) using the tec hnique of in vitro selection to generate variants that are resistant to did anosine and/or stavudine. After serial passages of the Lai strain of HIV1 i n MT-2 cells in increased concentrations of didanosine-stavudine associatio n, 2 novel mutations in reverse transcriptase at codon 57 (Asp->His) and at codon 98 (Ala-->Val) were observed. These mutations were associated with a n 11.5-fold increase in the didanosine and a 4.5-fold increase in the stavu dine 50% inhibitory concentration.