NDLI: Characterization of the E138K resistance mutation in HIV-1 reverse transcriptase conferring susceptibility to etravirine in B and non-B HIV-1 subtypes.

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Characterization of the E138K resistance mutation in HIV-1 reverse transcriptase conferring susceptibility to etravirine in B and non-B HIV-1 subtypes.

Content Provider	Semantic Scholar
Author	Asahchop, Eugene L. Oliveira, Maureen Wainberg, Mark A. Brenner, Bluma G. Moisi, Daniela Toni, Thomas D'Aquin Tremblay, Cécile L.
Copyright Year	2011
Abstract	We have selected for resistance to etravirine (ETR) and efavirenz (EFV) in tissue culture using three subtype B, three subtype C, and two CRF02_AG clinical isolates, grown in cord blood mononuclear cells. Genotypic analysis was performed at baseline and at various weeks of selection. Phenotypic resistance in regard to ETR, EFV, and nevirapine (NVP) was evaluated at weeks 25 to 30 for all ETR-selected viruses and in viral clones that contained specific resistance mutations that were inserted by site-directed mutagenesis into pNL-4.3 and AG plasmids. The results show that ETR selected mutations at positions V90I, K101Q, E138K, V179D/E/F, Y181C, V189I, G190E, H221H/Y, and M230L and that E138K was the first of these to emerge in most instances. The time to the emergence of resistance was longer in the case of ETR (18 weeks) compared to EFV (11 weeks), and no differences in the patterns of emergent mutations could be documented between the B and non-B subtypes. Viral clones containing E138K displayed low-level phenotypic resistance to ETR (3.8-fold) and modestly impaired replication capacity (2-fold) compared to wild-type virus. ETR-selected virus showed a high degree of cross-resistance to NVP but not to EFV. We identified K101Q, E138K, V179E, V189I, G190E, and H221Y as mutations not included among the 17 currently recognized resistance-associated mutations for ETR.
File Format	PDF HTM / HTML
DOI	10.1128/AAC.01192-10
Alternate Webpage(s)	http://www.natap.org/2012/HIV/AntimicrobAgentsChemother2011Asahchop6007.pdf
PubMed reference number	21135184
Alternate Webpage(s)	https://doi.org/10.1128/AAC.01192-10
Journal	Medline
Volume Number	55
Issue Number	2
Journal	Antimicrobial agents and chemotherapy
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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