Resistance profiles of (+)2'-deoxy-3'-oxa-4'-thiocytidine and (-)2'-deoxy-3'-oxa-4'-thio-5-fluorocytidine.
Resistant variants were selected in vitro against two novel nucleoside analogues, (+) dOTC and (-) dOTFC using the HIV-1 molecular clone HXB2D. The variants obtained displayed 6.5-fold and 10-fold resistance to these compounds, respectively. Cloning and sequencing of the RT genes of the selected viruses identified two mutations, M184I for (+) dOTC and M184V for (-) dOTFC. Results with mutated recombinant clones of HXB2D confirmed the importance of these mutations in MT-4 cells. The resistance profiles of clinical samples with wild-type or 3TC-resistant phenotypes were also studied; low to moderate levels of cross-resistance were observed against the novel compounds.
Richard
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N
McGill University AIDS Centre, Jewish General Hospital, Montreal, Quebec, Canada.
Salomon
H
H
Oliveira
M
M
Rando
R
R
Wainberg
M A
MA
D019380:Anti-HIV Agents / Q000494:pharmacology*; D002460:Cell Line; D003562:Cytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008826:Microbial Sensitivity Tests; D013872:Thionucleosides / Q000494:pharmacology*
C120719:2'-deoxy-3'-oxa-thiocytidine; D019380:Anti-HIV Agents; D013872:Thionucleosides; D003841:Deoxycytidine; C081758:2'-deoxy-5-fluoro-3'-thiacytidine; D003562:Cytidine; D054303:HIV Reverse Transcriptase