Generation of drug-resistant variants of human immunodeficiency virus type 1 by in vitro passage in increasing concentrations of 2',3'-dideoxycytidine and 2',3'-dideoxy-3'-thiacytidine.
We selected in vitro human immunodeficiency virus type 1 variants that are resistant to each of 2',3'-dideoxycytidine (ddC) and the racemic mixture of 2',3'-dideoxy-3'-thiacytidine (BCH-189). The median effective concentrations of ddC and BCH-189 obtained for the resistant viruses ranged between 10 and 50 times above those for parental wild-type strains, and extensive cross-resistance was observed against 2',3'-dideoxyinosine (ddI) but not 3'-azido-3'-deoxythymidine (AZT). Two dimer compounds, in which either AZT and ddI or AZT and BCH-189 were linked through phosphodiester linkages, did not permit the emergence of variants resistant to BCH-189, ddI, or AZT but were ineffective at inhibiting the replication of AZT-resistant viruses.
Lady Davis Institute-Jewish General Hospital, Montreal, Quebec, Canada.
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Wainberg
D000163:Acquired Immunodeficiency Syndrome / Q000382:microbiology; D000998:Antiviral Agents / Q000494:pharmacology*; D004351:Drug Resistance; D015658:HIV Infections / Q000382:microbiology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D019259:Lamivudine; D016047:Zalcitabine / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000998:Antiviral Agents; D019259:Lamivudine; D016047:Zalcitabine