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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 <3-fold-decreased susceptibility to nevirapine or efavirenz. Combinations of Y318F with K103N, Y181C, or both resulted in decreased efavirenz susceptibility of 43-, 3.3-, and 84-fold, respectively, as well as >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.

Original publication

DOI

10.1128/jvi.76.13.6836-6840.2002

Type

Journal article

Journal

J Virol

Publication Date

07/2002

Volume

76

Pages

6836 - 6840

Keywords

3' Untranslated Regions, Anti-HIV Agents, Drug Resistance, Viral, HIV Reverse Transcriptase, HIV-1, Humans, Microbial Sensitivity Tests, Models, Molecular, Mutagenesis, Site-Directed, Mutation, Reverse Transcriptase Inhibitors