Long-term persistence of AZT-resistance mutations in the plasma HIV-1 of patients removed from AZT therapy.

Zidovudine (3'-azido-2',3'-dideoxythymidine) resistant isolates of human immunodeficiency virus type I (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 (PCR) amplification of plasma culture DNA. The zidovudine-resistance mutations persisted in seven timepoints from four patients for 5 to 22 months despite cessation of zidovudine therapy (and while patients underwent ddI therapy). One patient's plasma virus isolate at 14 months possessed a genotype doubly resistant to ZDV and ddI. Virus recovered from four timepoints 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.