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.
Introduction: The Q148 H mutation in combination with the G140 S secondary mutation confers the highest level of resistance to RAL (> 1000-fold) together with the highest replicative capacity in vitro .
Extended use of raltegravir in the treatment of HIV-1 infection: optimizing therapy.
Discussion: Among raltegravir-resistant double mutants, the highest selective-advantage profile was seen with G140S + Q148H.
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: The secondary mutations G140A/S, E92Q, and T97A are preferentially linked to the Q148, N155, and Y143 genetic pathways, respectively.
Secondary mutations in viruses resistant to HIV-1 integrase inhibitors that restore viral infectivity and replication kinetics.
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: Secondary amino acid substitutions E138K or G140S were observed when passage with INI was continued.
G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not.
Abstract: Altogether, these results account for the predominance of G140S/Q148H mutants in clinical trials using Raltegravir.
Abstract: By contrast, the conformational transition converting the inactive form into an active form is rescued by the G140S/Q148H double mutation.
Abstract: In conclusion, the Q148H mutation is responsible for resistance to Raltegravir whereas the G140S mutation increases viral fitness in the G140S/Q148H context.
Abstract: We found that (i) integration is impaired for Q148H when compared with the wild-type, G140S and G140S/Q148H
HIV-1 integrase polymorphisms are associated with prior antiretroviral drug exposure.
Introduction: G140S was not documented by Rhee et al.
Introduction: However, both G140S mutations in our study occurred in samples from previously ARV-treated individuals, suggesting that previous therapy may result in reduced INI efficacy, and further supporting IN sequencing in patients contemplating INI therapy initiation.
Introduction: However, in a small study conducted at Westmead Hospital, Sydney, Australia, G140S was detected in 2 INI-naive patients, as were the other accessory mutations: L74I/M (n = 8), T97A (n = 2), V151I (n = 3) and I203M (n = 4).
Introduction: In contrast, i
Quasispecies variant dynamics during emergence of resistance to raltegravir in HIV-1-infected patients.
PMID: 19221102
2009
The Journal of antimicrobial chemotherapy
Abstract: We observed a greater variability among quasispecies associated with the 155 pathway, and IC(50) determinations showed that the fold resistance to raltegravir, relative to wild-type, was 10 for the N155H mutant and 50 for the G140S+Q148H mutant.
Characterization and structural analysis of HIV-1 integrase conservation.
Abstract: Nevertheless, at positions 140 and 151, the variability between subtypes affected the genetic barrier for the mutations G140C, G140S and V1511 with a higher genetic barrier being calculated for subtype CRF02_AG.
Selective-advantage profile of human immunodeficiency virus type 1 integrase mutants explains in vivo evolution of raltegravir resistance genotypes.
Abstract: Among double mutants, the highest and widest selective-advantage profile was seen with G140S+Q148H.
HIV-1 IN alternative molecular recognition of DNA induced by raltegravir resistance mutations.
PMID: 19623602
2009
Journal of molecular recognition
Abstract: Virologic failure during treatment with raltegravir, the first effective drug targeting HIV integrase, is associated with two exclusive pathways involving either Q148H/R/K, G140S/A or N155H mutations.
HIV mutation literature information.
PMID: 
2010
Retrovirology
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