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
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.
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.
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
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.
Switching between raltegravir resistance pathways analyzed by deep sequencing.
Introduction: Three codons can mutate to generate primary resistance mutations, which encode Y143R/C/H, Q148H
Discussion: Our findings taken together support the idea that Y143H, and possibly Y143C and Q148R, are authentic replication-competent polymorphisms that are present in viral populations in the absence of RAL.
Discussion: The Y143C and Q148R substitutions were marginally significant by some measures but did not survive correction for multiple comparisons.
Discussion: also investigated RAL resistance using 454 sequencing and reported detection of Y143H, Y143C, and Q148R prior to initiation of therapy.
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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