Susceptibilities of human immunodeficiency virus type 1 enzyme and viral variants expressing multiple resistance-engendering amino acid substitutions to reserve transcriptase inhibitors.
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.
Byrnes
V W
VW
Merck Research Laboratories, West Point, Pennsylvania 19486.
Emini
E A
EA
Schleif
W A
WA
Condra
J H
JH
Schneider
C L
CL
Long
W J
WJ
Wolfgang
J A
JA
Graham
D J
DJ
Gotlib
L
L
Schlabach
A J
AJ
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
D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D054303:HIV Reverse Transcriptase