title: Human immunodeficiency virus type 1 recombinant reverse transcriptase enzymes containing the G190A and Y181C resistance mutations remain sensitive to etravirine.
abstract: Etravirine (ETR) is a second-generation nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI) active against common human immunodeficiency virus type 1 (HIV-1) drug-resistant strains. This study was designed to determine the extent to which each of the Y181C or G190A mutations in RT might confer resistance to ETR and other members of the NNRTI family of drugs. Recombinant HIV-1 RT enzymes containing either the Y181C or the G190A mutation, or both mutations in tandem, were purified. Both RNA- and DNA-dependent DNA polymerase assays were performed in order to determine the extent to which each of these mutations might confer resistance in cell-free biochemical assays against each of ETR, efavirenz, and nevirapine. Both the biochemical and the cell-based phenotypic assays confirmed the susceptibility of G190A-containing enzymes and viruses to ETR. The results of this study indicate that the G190A mutation is not associated with resistance to ETR.
authors.affiliation: McGill University AIDS Centre, Lady Davis Institute for Medical Research. Jewish General Hospital, 3755 Cote Ste. Catherine Rd., Montreal, Quebec, Canada H3T 1E2.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Xu
authors.forename: Yudong
authors.initials: Y
authors.lastname: Quan
authors.forename: Bluma G
authors.initials: BG
authors.lastname: Brenner
authors.forename: Tamara
authors.initials: T
authors.lastname: Bar-Magen
authors.forename: Maureen
authors.initials: M
authors.lastname: Oliveira
authors.forename: Susan M
authors.initials: SM
authors.lastname: Schader
authors.forename: Mark A
authors.initials: MA
authors.lastname: Wainberg
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000235:genetics*; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009570:Nitriles; D011724:Pyridazines / Q000494:pharmacology*; D011743:Pyrimidines; D011994:Recombinant Proteins / Q000235:genetics / Q000302:isolation & purification; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors; C451734:etravirine; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase
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