title: The genetic and functional basis of HIV-1 resistance to nonnucleoside reverse transcriptase inhibitors.
abstract: The nonnucleoside reverse transcriptase (RT) inhibitors are structurally diverse compounds that are specific inhibitors of the human immunodeficiency virus type 1 RT enzyme. The compounds are largely functionally identical and bind to a common site in the enzyme. HIV-1 variants that exhibit reduced susceptibility to these inhibitors have been derived in cell culture and, more recently, from HIV-1-infected patients undergoing experimental therapy. The variants express amino acid substitutions at RT positions that apparently interact directly with the inhibitors. Effects of specific substitutions at these positions vary among the compounds, suggesting subtle differences in how the compounds physically interact with the enzyme.
authors.affiliation: Merck Research Laboratories, West Point, Pennsylvania.
authors.forename: E A
authors.initials: EA
authors.lastname: Emini
authors.forename: V W
authors.initials: VW
authors.lastname: Byrnes
authors.forename: J H
authors.initials: JH
authors.lastname: Condra
authors.forename: W A
authors.initials: WA
authors.lastname: Schleif
authors.forename: V V
authors.initials: VV
authors.lastname: Sardana
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology; D001583:Benzoxazoles / Q000494:pharmacology; D002986:Clinical Trials as Topic; D004352:Drug Resistance, Microbial / Q000235:genetics; D014644:Genetic Variation; D015658:HIV Infections / Q000188:drug therapy; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D019829:Nevirapine; D011725:Pyridines / Q000494:pharmacology; D011728:Pyridones / Q000494:pharmacology; D012194:RNA-Directed DNA Polymerase / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors
chemical_list: D000998:Antiviral Agents; D001583:Benzoxazoles; D007093:Imidazoles; D011725:Pyridines; D011728:Pyridones; D018894:Reverse Transcriptase Inhibitors; D001569:Benzodiazepines; C076250:L 696229; C076516:L-697661; C067413:R-82913; D019829:Nevirapine; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase