NDLI: Identification of a rare mutation at reverse transcriptase Lys65 (K65E) in HIV-1-infected patients failing on nucleos(t)ide reverse transcriptase inhibitors.

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Identification of a rare mutation at reverse transcriptase Lys65 (K65E) in HIV-1-infected patients failing on nucleos(t)ide reverse transcriptase inhibitors.

Content Provider	Semantic Scholar
Author	Fourati, Slim Visseaux, Benoît Armenia, Daniele Morand-Joubert, Laurence Artese, Anna Charpentier, Charlotte Eede, Peter Van Den Costa, Giosuè Alcaro, Stefano Wirden, Marc Perno, Carlo Federico Silberstein, Francesca Ceccherini Descamps, Diane Calvez, Vincent Marcelin, Anne-geneviève
Copyright Year	2013
Abstract	OBJECTIVES The HIV reverse transcriptase (RT) mutation K65R confers resistance to nucleos(t)ide reverse transcriptase inhibitors (NRTIs). Here, analysing a large database, we report the selection of another rare K65E mutation in patients failing on NRTI-containing regimens. METHODS Clinical and virological characteristics of patients harbouring the K65E mutation were analysed using a large RT sequence database from treatment-experienced individuals. Structural analysis of the K65E RT mutant complex was performed by means of docking simulations. The replication capacity was assessed using viruses harbouring the K65E mutation introduced by site-directed mutagenesis (SDM) in pNL 4-3. RESULTS Overall, in 23 530 sequences from patients failing on antiretroviral therapy, the prevalence of substitutions at position K65 in RT was 2.4%. In addition to K65R (n = 395) and K65N (n = 9), another mutation, K65E, was found in 15 patients. In 11 out of 15 cases, tenofovir, abacavir, didanosine or stavudine were present at the time of K65E selection. The molecular recognition of RT containing K65E supports evidence for the role of this mutation in resistance to tenofovir. The SDM pNL4-3 K65E variant harboured a very low replicative capacity (5% versus wild-type). CONCLUSIONS We investigated the role of a novel rare NRTI mutation located at position Lys65 of RT (K65E), found in drug-experienced patients failing on NRTIs. The low frequency of this mutation is probably related to the high impairment of replicative capacity induced by this mutation. This study should have significant clinical implications, as these findings warn clinicians that other minor substitutions at Lys65 (such as K65E) play a role in NRTI resistance.
Starting Page	394
Ending Page	408
Page Count	15
File Format	PDF HTM / HTML
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PubMed reference number	23749955v1
Alternate Webpage(s)	https://doi.org/10.1093/jac/dkt200
DOI	10.1093/jac/dkt200
Journal	The Journal of antimicrobial chemotherapy
Volume Number	68
Issue Number	10
Language	English
Access Restriction	Open
Subject Keyword	Antiretroviral therapy Didanosine HIV Reverse Transcriptase Mutagenesis, Site-Directed Mutation Nucleoside Reverse Transcriptase Inhibitor Patients RNA-Directed DNA Polymerase Reverse Transcriptase Inhibitors Reverse Transcriptase Polymerase Chain Reaction Stavudine Tenofovir abacavir
Content Type	Text
Resource Type	Article

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Identification of a rare mutation at reverse transcriptase Lys65 (K65E) in HIV-1-infected patients failing on nucleos(t)ide reverse transcriptase inhibitors

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