title: Susceptibilities of human immunodeficiency virus type 1 enzyme and viral variants expressing multiple resistance-engendering amino acid substitutions to reserve transcriptase inhibitors.
abstract: To evaluate the potential that multiply resistant human immunodeficiency virus type 1 variants may arise during combination nucleoside and nonnucleoside reverse transcriptase inhibitor therapy, we constructed a series of mutant reverse transcriptase enzymes and viruses that coexpressed various combinations of resistance-associated amino acid substitutions. Substitutions at residues 100 (Leu-->Ile) and 181 (Tyr-->Cys), which mediate resistance to the nonnucleosides, suppressed resistance to 3'-azido-3'-deoxythymidine (AZT) when coexpressed with AZT-specific substitutions. However, a number of viral variants that exhibited significantly reduced susceptibilities to both classes of inhibitors were constructed.
authors.affiliation: Merck Research Laboratories, West Point, Pennsylvania 19486.
authors.forename: V W
authors.initials: VW
authors.lastname: Byrnes
authors.forename: E A
authors.initials: EA
authors.lastname: Emini
authors.forename: W A
authors.initials: WA
authors.lastname: Schleif
authors.forename: J H
authors.initials: JH
authors.lastname: Condra
authors.forename: C L
authors.initials: CL
authors.lastname: Schneider
authors.forename: W J
authors.initials: WJ
authors.lastname: Long
authors.forename: J A
authors.initials: JA
authors.lastname: Wolfgang
authors.forename: D J
authors.initials: DJ
authors.lastname: Graham
authors.forename: L
authors.initials: L
authors.lastname: Gotlib
authors.forename: A J
authors.initials: AJ
authors.lastname: Schlabach
mesh_terms: D004352:Drug Resistance, Microbial; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects*; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors; D013329:Structure-Activity Relationship; D015215:Zidovudine / Q000494:pharmacology
chemical_list: D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D054303:HIV Reverse Transcriptase