Abstract: Thirteen patients failed raltegravir (RAL)-containing regimens within 8 +- 1 months, in association with the major Q148K/R/H and G140A/S (n = 8/24) or N155H (n = 5/24) mutational pathways.
Resistance to raltegravir highlights integrase mutations at codon 148 in conferring cross-resistance to a second-generation HIV-1 integrase inhibitor.
Abstract: This was confirmed by phenotypic analysis of 766 clonal viruses harboring IN sequences isolated at the point of virological failure from 106 patients on HAART (including RAL), where mutation Q148H/K/R together with additional secondary mutations conferred reduced susceptibility to both RAL and MK-2048.
Switching between raltegravir resistance pathways analyzed by deep sequencing.
Introduction: Specifically, the N155H pathway is commonly replaced by the Q148H/R/K pathway, resulting in reduced susceptibility to RAL and improved viral replication capacity.
Introduction: Three codons can mutate to generate primary resistance mutations, which encode Y143R/C/H, Q148H/R/K, and N155H.
Result: After 3 months of therapy, N155H, Q148K, and Q148R all coexisted (Figs 2a and 3b).
Result: The Q148K + E138K combination was evident at month 3, and though this combination is reported to be a potent RAL escape variant, it was not detected subsequently.
G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not.
Introduction: The virological failure of RAL-based treatment in HIV-1 infection is associated primarily with the initial, independent development of the principal N155H and Q148H/K/R pathways, either alone or together with other resistance mutations.
Discussion: The concomitant selection of the Q148H/R/K and G140S mutations in both HIV-1 and HIV-2 RAL-resistant viruses is grounded in the structure of IN, indicating a close interaction between these two residues that are conserved in retroviral IN.
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.
The HIV-1 integrase genotype strongly predicts raltegravir susceptibility but not viral fitness of primary virus isolates.
Abstract: OBJECTIVE: : Resistance to raltegravir is associated with three genetic pathways defined by the mutations Y143R/C, Q148H/R/K or N155H in integrase, which also infer a viral fitness cost.
A dynamic model of HIV integrase inhibition and drug resistance.
Abstract: Resistance to raltegravir (RAL), the first HIV-1 integrase (IN) inhibitor approved by the FDA, involves three genetic pathways: IN mutations N155H, Q148H/R/K, and Y143H/R/C.
Natural polymorphisms of integrase among HIV type 1-infected South African patients.
PMID: 20377427
2010
AIDS research and human retroviruses
Abstract: Amino acid sequence analysis revealed there were no primary mutations (Y143R/C/H, Q148H/R/K, and N155H/S) associated with reduced susceptibility to the integrase inhibitors raltegravir and elvitegravir.
Primary mutations selected in vitro with raltegravir confer large fold changes in susceptibility to first-generation integrase inhibitors, but minor fold changes to inhibitors with second-generation resistance profiles.
HIV mutation literature information.
PMID: 
2011
Journal of medical virology
Browser Board
Co-occurred Entities
Filtrator
ViMRT