LONG-TERM PERSISTENCE OF ZIDOVUDINE RESISTANCE MUTATIONS IN PLASMA ISOLATES OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 OF DIDEOXYINOSINE-TREATED PATIENTS REMOVED FROM ZIDOVUDINE THERAPY

Zidovudine (3'-azido-2',3'-dideoxythymidine)-resistant isolates of human immunodeficiency virus type 1 (HIV-1) were previously demonstrated in zidovudine-treated AIDS patients. The genetic linkage of multiple mutations characteristic of zidovudine resistance as well as dideoxyinosine resistance were demonstrated by examining clones of viral reverse transcriptase after polymerase chain reaction amplification of plasma culture DNA. The zidovudine resistance mutations persisted at seven time points from 4 patients for 5-22 months despite cessation of zidovudine therapy (and while patients underwent dideoxyinosine therapy). One patient's plasma virus isolate at 14 months possessed a genotype doubly resistant to zidovudine and dideoxyinosine. Virus recovered from four time points showed intermediate to high levels of zidovudine resistance. As these genotypes were mainly derived from plasma culture, the zidovudine-resistant virus appears to persist and replicate well in vivo after cessation of zidovudine therapy.