Introduction: In vitro, several mutations have been introduced into the IN gene and activities of mutants have been determined (T66I, L74M, E92Q, F121Y, Q148K, S153Y, N155H).
Introduction: The most frequent primary RAL resistance mutations emerging in vivo at virological failure (VF) in the IN gene are Q148H/R/K, N155H, and to a lesser extent Y143C/H/R.
Method: We followed-up the 50 mutations of resistance present at 32 positions: associated with in vitro or in vivo resistance to HIV-1 integrase inhibitors:
Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness.
PMID: 20634701
2010
Journal of acquired immune deficiency syndromes (1999)
Result: Similarly the Q148K and R mutants were less fit than WT in the absence of RAL and more fit than WT in the presence of drug (Table 2).
Result: The Q148R and Q148K mutants were fitter than the N155H mutant in absence of drug, but less fit in the presence of 5.0 microM RAL (data not shown).
Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors.
Introduction: In most patients, mutations in IN responsible for RAL failure are represented in two independent genetic pathways; N155H and Q148H/R/K accounting for a severe loss (10-25 fold) in susceptibility to RAL with additional secondary mutations.
Discussion: An in-silico study of N155H and Q148H/R/K demonstrated that the structure of flexible loop (residues 140-148) in catalytic domain is conserved suggesting IN would be catalytically active.
Discussion: Comprehensive in vitro mutagenesis and computational studies of the flexible loop in HIV-1 IN accounted for most of the observed phenotypes of N155H and Q148H/R/K mutations in
Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir.
Introduction: In HIV-1-infected patients failing an INI-containing regimen, three distinct resistance pathways involving Y143R, Q148H/R/K or N155 H have been described.
Introduction: RAL resistance is not well documented for HIV-2, although cases of therapy failure have been associated with the emergence of variants carrying the Y143C, Q148K/R, or N155 H mutations, including Y143Y+T97A or Q148K, or Q148R+G140 S.
Extended use of raltegravir in the treatment of HIV-1 infection: optimizing therapy.
Abstract: The development of resistance to raltegravir mainly involved three resistance mutations in integrase gene: Q148H/K/R, N155H, and Y143C/H/R.
Discussion: Of the 11 assessable patients who displayed a viral rebound on raltegravir-based therapy, virus with mutations known to confer raltegravir resistance was found in eight patients: N155H (n = 6); Q148H/K/R +- G140S (n = 2); Y143C (n = 1).
Discussion: Several studies reported that these primary resistance mutations Y143C/R, Q148H/K/R, and N155H represent mutually exclusive and nonoverlappi
Secondary mutations in viruses resistant to HIV-1 integrase inhibitors that restore viral infectivity and replication kinetics.
Abstract: Integrase-resistant mutations Q148K and Q148R were identified as primary mutations with the passage of HIV-1 IIIB in the presence of INIs S-1360 or S/GSK-364735, respectively.
Abstract: In contrast, Q148K/G140S and Q148R/E138K had nearly equivalent or slightly reduced fold resistance to the INI compared with their respective Q148 primary mutants, and had increases in infectivity and replication kinetics.
Abstract: Relative to Q148K alone, Q148K/E138K had 2- and >6-fold increases in resistance to S-1360 and S/GSK-364735, respectively, and the double muta
The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation.
Discussion: Mutants Q148K/R displayed reduced viral fitness whatever the cell line studied (PBMC or Jurkat cells).
Discussion: The authors have studied the Q148K/R and G140S mutations as well as the G140S/Q148R and G140S/Q148K double mutants.
Discussion: and our study show that the G140S mutation rescues the ability of the Q148H/K/R mutants to replicate in cells while mutation of the Q148 residue is responsible for the resistance to the drug.
Discussion: have shown that the G140S mutation rescues the fitness of the Q148K/R mutant.
HIV-1 integrase polymorphisms are associated with prior antiretroviral drug exposure.
Introduction: These occur in one of two main pathways, either N155H or Q148H/K/R.
Introduction: in their review of the Stanford HIV Database in only 3 isolates (each with a single primary INI mutation N155H, Q148H and Q148K).
Quasispecies variant dynamics during emergence of resistance to raltegravir in HIV-1-infected patients.
PMID: 19221102
2009
The Journal of antimicrobial chemotherapy
Abstract: In most patients, raltegravir failure is associated with mutations in the IN gene, through two different genetic pathways: 155 (N155H) or 148 (Q148K/R/H).
Lack of primary mutations associated with integrase inhibitors among HIV-1 subtypes B, C, and F circulating in Brazil.
PMID: 19262402
2009
Journal of acquired immune deficiency syndromes (1999)
Abstract: Major mutations associated with elvitegravir or raltegravir in vivo resistance (Q148K/H/R, N155H) were not detected.
HIV mutation literature information.
PMID: 
2010
PloS one
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