Biological comparison of wild-type and zidovudine-resistant isolates of human immunodeficiency virus type 1 from the same subjects: susceptibility and resistance to other drugs.
We used a viral endpoint dilution assay to show changes in the proportion of zidovudine (azidothymidine; AZT)-resistant viruses within a heterogeneous mixture of human immunodeficiency virus type 1 (HIV-1) quasispecies isolated from patients on long-term AZT therapy. Several HIV-1 isolates, which could replicate in 10 microM AZT, were susceptible to both 2',3'-dideoxycytidine and a novel cytosine analog BCH-189, in which a sulfur atom replaces the 3' carbon of the pentose ring. In certain instances, cross-resistance was seen with 3'-didehydro-2',3'-dideoxythymidine. Although most strains of AZT-resistant HIV-1 displayed reduced susceptibility to 3'-azido-2',3'-dideoxyuridine, two strains were identified for which this was not the case.
Rooke
R
R
Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada.
Parniak
M A
MA
Tremblay
M
M
Soudeyns
H
H
Li
X G
XG
Gao
Q
Q
Yao
X J
XJ
Wainberg
M A
MA
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000382:microbiology; D000998:Antiviral Agents / Q000494:pharmacology; D003596:Cytosine / Q000031:analogs & derivatives / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D019259:Lamivudine; D009705:Nucleosides / Q000494:pharmacology; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000187:drug effects; D016047:Zalcitabine / Q000494:pharmacology; D015215:Zidovudine / Q000494:pharmacology*
D000998:Antiviral Agents; D009705:Nucleosides; D019259:Lamivudine; D015215:Zidovudine; D016047:Zalcitabine; D003596:Cytosine