title: Resistance profiles of (+)2'-deoxy-3'-oxa-4'-thiocytidine and (-)2'-deoxy-3'-oxa-4'-thio-5-fluorocytidine.
abstract: 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.
authors.affiliation: McGill University AIDS Centre, Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Richard
authors.forename: H
authors.initials: H
authors.lastname: Salomon
authors.forename: M
authors.initials: M
authors.lastname: Oliveira
authors.forename: R
authors.initials: R
authors.lastname: Rando
authors.forename: M A
authors.initials: MA
authors.lastname: Wainberg
mesh_terms: 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*
chemical_list: 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