A Mutation in the 3′ Region of the Human Immunodeficiency Virus Type 1 Reverse Transcriptase (Y318F) Associated with Nonnucleoside Reverse Transcriptase Inhibitor Resistance
- 1 July 2002
- journal article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 76 (13) , 6836-40
- https://doi.org/10.1128/jvi.76.13.6836-6840.2002
Abstract
The Y318F substitution in the 3' region of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) has been linked to nonnucleoside RT inhibitor (NNRTI) resistance in vitro. A systematic search of a large phenotypic-genotypic database (Virco) linked the Y318F substitution with a >10-fold decrease in NNRTI susceptibility in >85% of clinically derived isolates. There was a significant association between Y318F and use of delavirdine (P = 10(-11)) and nevirapine (P = 10(-6)) but not efavirenz (P = 0.3). Site-directed HIV-1 Y318F mutants in an HXB2 background displayed 42-fold-decreased susceptibility to delavirdine but 100- and >60-fold decreases in delavirdine and nevirapine susceptibility, respectively. These results indicate the importance of the Y318F substitution in HIV-1 drug resistance.Keywords
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