       Document 0810
 DOCN  M94B0810
 TI    Susceptibilities of human immunodeficiency virus type 1 enzyme and viral
       variants expressing multiple resistance-engendering amino acid
       substitutions to reserve transcriptase inhibitors.
 DT    9412
 AU    Byrnes VW; Emini EA; Schleif WA; Condra JH; Schneider CL; Long WJ;
       Wolfgang JA; Graham DJ; Gotlib L; Schlabach AJ; et al; Merck Research
       Laboratories, West Point, Pennsylvania 19486.
 SO    Antimicrob Agents Chemother. 1994 Jun;38(6):1404-7. Unique Identifier :
       AIDSLINE MED/94379800
 AB    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.
 DE    Drug Resistance, Microbial  HIV-1/*DRUG EFFECTS  Mutation  Reverse
       Transcriptase/*ANTAGONISTS & INHIB  Structure-Activity Relationship
       Zidovudine/PHARMACOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

