DEVELOPMENT OF ZIDOVUDINE RESISTANCE MUTATIONS IN PATIENTS RECEIVING PROLONGED DIDANOSINE MONOTHERAPY

Human immunodeficiency virus type 1 (HIV-1) isolates from 2 patients w ho received didanosine (ddI) monotherapy for >2 years were analyzed fo r reverse transcriptase (RT) mutations by sequencing of proviral DNA f rom peripheral blood mononuclear cell cultures. One patient was otherw ise antiretroviral-naive; the other had received zidovudine for 5 mont hs before beginning ddI therapy. Isolates obtained from both patients before initiation of ddI monotherapy were free of HIV-1 RT mutations a ssociated with zidovudine or ddI resistance, However, after prolonged ddI monotherapy, mutations associated with zidovudine resistance (M41L , D67N, K70R, and/or T215Y) were detected in HIV-1 isolates from both patients. There was no evidence that surreptitious use of zidovudine o r technical artifact caused these findings. This observation suggests that prolonged ddI monotherapy may decrease the efficacy of subsequent zidovudine therapy in some patients.