Antiviral activity and resistance profile of phosphazid--a novel prodrug of AZT.
Both AZT and its novel 5'-hydrogen phosphonate derivative, Phosphazid, possess similar in vitro activity and resistance profiles. Experiments involving AZT-resistant virus isolates revealed a strong correlation between resistance to AZT and cross-resistance to Phosphazid. In vitro selection for resistance to Phosphazid yielded viruses that were about 15-fold less sensitive than wild-type virus to this drug. Sequencing of the reverse transcriptase region of seven Phosphazid-selected viruses revealed a single codon mutation, D67N, that is associated with resistance to AZT.
Machado
J
J
McGill University AIDS Centre, Jewish General Hospital, Montreal, Quebec, Canada.
Salomon
H
H
Oliveira
M
M
Tsoukas
C
C
Krayevsky
A A
AA
Wainberg
M A
MA
D019380:Anti-HIV Agents / Q000494:pharmacology*; D002460:Cell Line; D004352:Drug Resistance, Microbial; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D009154:Mutation; D063065:Organophosphonates / Q000494:pharmacology*; D011355:Prodrugs / Q000494:pharmacology*; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000494:pharmacology
C000604073:3'-azido-2',3'-dideoxythymidine 5'-H-phoshonate; D019380:Anti-HIV Agents; D063065:Organophosphonates; D011355:Prodrugs; D015215:Zidovudine