Abstract: Signature HIV-1 integrase mutations associated with clinical raltegravir resistance involve 1 of 3 primary genetic pathways, Y143C/R, Q148H/K/R and N155H, the latter 2 of which confer cross-resistance to elvitegravir.
Discussion: Dolutegravir maintains prolonged binding with the Y143C/H/R mutants as demonstrated by dissociative t1/2 values of 42 to 60 hours.
Discussion: Note, from Table S1 in File S1, however, that EVG's dissociative t1/2 values with Y143C/H/R, which range from 1.6 to 2.1 hours, are comparable in magnitude to those of RAL, yet EVG has near wild-type antiviral activity.
Discussion: The 4.4-, 3.5- and 8-fold decreases in RAL's dissociative t1/2 caused by the Y
Multiple genetic pathways involving amino acid position 143 of HIV-1 integrase are preferentially associated with specific secondary amino acid substitutions and confer resistance to raltegravir and cross-resistance to elvitegravir.
PMID: 23733474
2013
Antimicrobial agents and chemotherapy
Abstract: Among Y143A,C,G,H,S viruses, the higher prevalence of Y143C viruses is the result of a lower genetic barrier than that of the Y143A,G,S viruses and a lower resistance barrier than that of the Y143H viruses.
Abstract: Here we describe clinical isolates with alternative substitutions at position 143 (Y143A, Y143G, Y143H, and Y143S [Y143A,G,H,S]) that emerge less frequently, and we compare the genotypic and phenotypic profiles of these viruses to Y143C,R viruses to reconcile the preferential selection of Y143C,R variants during RAL tre
Binding mode prediction of biologically active compounds from plant Salvia Miltiorrhiza as integrase inhibitor.
Introduction: The two primary resistance pathways involved mutations of the amino acids at Q148 (Q148K/R/H) or N155 (N155/H) whereas a third primary mutation pathway at Y143 (Y143C/R) was less commonly found .
Discussion: The proposed raltegravir resistance pathway of the less frequently Y143H/R/C has been directly related to the interaction between inhibitor and Tyr143.
In vitro phenotypes to elvitegravir and dolutegravir in primary macrophages and lymphocytes of clonal recombinant viral variants selected in patients failing raltegravir.
PMID: 23798668
2013
The Journal of antimicrobial chemotherapy
Abstract: No variations were observed for the Y143R/C (+/-T97A) or N155H variants.
Abstract: When compared with raltegravir, none to modest increases in resistance were observed for the Y143R/C pathways.
HIV-1 integrase resistance among antiretroviral treatment naive and experienced patients from Northwestern Poland.
Introduction: Virologic failure has been associated with major, signature mutations within the catalytic domain of the enzyme, and include Y143R/C, N155H Q148K/R/H integrase sequence variants associated with significant susceptibility reduction both to RAL and elvitegravir (EVG) .
"Prolonged and substantial discordance in prevalence of raltegravir-resistant HIV-1 in plasma versus PBMC samples revealed by 454 ""deep"" sequencing."
Introduction: Post-raltegravir-therapy evolution of raltegravir-associated DRMs in plasma samples is relatively well-characterized, with reports showing Q148H/K/R+G140S and N155H emerged before Y143R/H/C.
Introduction: Well-characterized mutations in the HIV-1 int region that confer high levels of resistance to raltegravir include E92Q, Y143R/H/C, Q148H/K/R and N155H.
Method: Out of the eight patients with DRMs, five of them developed at least one of the three major raltegravir resistance pathways (Y143R/C/H, Q148H/R/K and/or N15
Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens.
Abstract: Collectively, our data define three major mutational pathways to high-level raltegravir and elvitegravir resistance: i) E92Q+Y143C or T97A+Y143C, ii) G140S+Q148R, and iii) E92Q+N155H.
Introduction: These additional changes cooperate with Y143C, Q148R and N155H to produce more substantial declines in drug susceptibility.
Introduction: We previously showed that the single amino acid changes Q148R and N155H in HIV-2 integrase confer moderate resistance to raltegravir, whereas the
In-vivo selection of the mutation F121Y in a patient failing raltegravir containing salvage regimen.
Abstract: Different resistance mutations in HIV integrase from patients using these antiretroviral drugs have been described and G148H/R/K, N155H and less frequently Y143C/H/R are considered major resistant mutations to raltegravir.
G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not.
Abstract: CONCLUSION: This study confirms that HIV-2 resistance to RAL is due to the N155H, G140S/Q148R or E92Q/Y143C mutations.
Abstract: Conversely, Y143C alone did not confer resistance to RAL unless E92Q is also present.
Abstract: Finally, the Y143C mutation counteracts the resistance conferred by the N155H mutation, probably accounting for the lack of detection of these mutations together in a single genome.
Abstract: For Y143C to confer resistance in vitro, it must be accompanied by E92Q, which therefore plays a more important role in the HIV-2 context than in the HIV-1 context.
Genetic variation of the HIV-1 integrase region in newly diagnosed anti-retroviral drug-naive patients with HIV/AIDS in Korea.
PMID: 20946407
2011
Clinical microbiology and infection
Abstract: Major mutation sites in the integrase (E92Q, F121Y, G140A/S, Y143C/R, Q148H/R/K and N155H) were not detected, and only a few minor mutation sites (L74M, V151I, E157Q, V165I, I203M, S230N and D232N) were identified in 21 strains (28%).
HIV mutation literature information.
PMID: 
2013
PloS one
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