Abstract: We have developed several sulfonamide-containing analogs that enhance potency in cell-based HIV assays by more than two orders-of-magnitude and we describe several compounds that are more potent than raltegravir against the clinically relevant Y143R IN mutant.
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) .
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%).
Cross-resistance profile determination of two second-generation HIV-1 integrase inhibitors using a panel of recombinant viruses derived from raltegravir-treated clinical isolates.
PMID: 20956600
2011
Antimicrobial agents and chemotherapy
Abstract: Although samples with the Y143R/C mutation had reduced susceptibility to RAL, they remained susceptible to MK-2048 and compound G.
In Vitro antiretroviral properties of S/GSK1349572, a next-generation HIV integrase inhibitor.
PMID: 21115794
2011
Antimicrobial agents and chemotherapy
Abstract: S/GSK1349572 demonstrated activity against site-directed molecular clones containing the raltegravir-resistant signature mutations Y143R, Q148K, N155H, and G140S/Q148H (FCs, 1.4, 1.1, 1.2, and 2.6, respectively), while these mutants led to a high FC in the EC(50) of raltegravir (11- to >130-fold).
Structure-analysis of the HIV-1 integrase Y143C/R raltegravir resistance mutation in association with the secondary mutation T97A.
PMID: 21576445
2011
Antimicrobial agents and chemotherapy
Abstract: Assays without RAL suggested that the T97A mutation could rescue the catalytic activity which was impaired by the presence of the Y143C/R mutation.
Abstract: FCs of 18 and 100 were observed with the strand transfer assay for IN Y143C/T97A and Y143R/T97A mutations, with IC(50) of 0.625 muM and 2.5 muM, respectively.
Abstract: In these patients, the Y143C/R mutation was associated with the T97A mutation.
Abstract: Reigadas et al., PLoS One 5:e10311, 2010), we investigated the genetic pathway and the dynamics of emergence of the Y143C/R mutations in three patients failing RAL-containing regimens.|mg
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/R/K, and N155H.
Result: At month 12, Q148H was the majority but N155H was still detectable, whereas Y143R was not.
Result: Patient 2 was the only participant in whom Y143R and N155H were detectable at later time-points.
Result: We also detected T97A, an accessory mutation for Y143R, and L74M and E92Q, accessory mutations for N155H, from the forward read sets (data not shown).
G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not.
Introduction: The third pathway, involving the Y143R/C mutation, is less frequently observed and was identified after the N155 and Q148 pathways.
Discussion: Y143C/R has been described as a primary mutation for HIV-1 resistance to RAL.
MK-0536 inhibits HIV-1 integrases resistant to raltegravir.
PMID: 21876054
2011
Antimicrobial agents and chemotherapy
Abstract: It is also effective against INs that carry the three main RAL resistance mutations (Y143R, N155H, and to a lesser extent G140S-Q148H) and against the G118R mutant.
Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance.
Discussion: Generally, the amino acid changes that appear in conjunction with Q148H/K/R, N155H and Y143C/R augment the level of raltegravir resistance in HIV-1 and, in some cases, mitigate the fitness costs incurred by primary resistance-associated mutations.
Discussion: Studies of HIV-1 patients have identified three principal mutational patterns that emerge in response to raltegravir treatment: Q148H/K/R with or without G140S/A, N155H with or without E92Q and Y143C/R with or without T97A.
HIV mutation literature information.
PMID: 
2012
Bioorganic & medicinal chemistry letters
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