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 associated mutations to dolutegravir (S/GSK1349572) in HIV-infected patients--impact of HIV subtypes and prior raltegravir experience.
Abstract: E92Q and Q148H/R were only seen in raltegravir-experienced patients and exclusively infected with subtype B (1.9% vs. 0%, p=0.026, for E92Q and 12.6% vs. 0%, p<0.001, for Q148H/R).
Abstract: T124A was more frequent in INI-naive patients but E92Q and Q148H/R were only seen in raltegravir-experienced individuals.
Transmission of integrase strand-transfer inhibitor multidrug-resistant HIV-1: case report and response to raltegravir-containing antiretroviral therapy.
Abstract: The virus harboured INI drug resistance substitutions (Q148H and G140S) along with multiple reverse transcriptase and protease inhibitor resistance mutations.
Single mutations in HIV integrase confer high-level resistance to raltegravir in primary human macrophages.
PMID: 21628534
2011
Antimicrobial agents and chemotherapy
Abstract: We show here that during macrophage infection, the presence of a single primary raltegravir resistance mutation (Q148H, Q148R, N155H, or N155S) is sufficient to provide resistance to raltegravir comparable to that seen in viruses expressing both primary and secondary mutations in costimulated CD4(+) T cells.
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.
Abstract: No reads contained both the N155H and Q148H drug resistance mutations (DRMs), indicating that the double mutant is not a prominent intermediate, consistent with low fitness.
Abstract: RESULTS: All three patients showed transitions from the
Discussion: Similarly for Q148H, the major form at the last time-point, only three reads were detected, a number also attributable to error.
Discussion: This is consistent with the idea that viruses with N155H or Q148H substitutions are considerably less fit than wild-type and so are very low in abundance in the absence of pressure from RAL.
Discussion: We analyzed the evolutionary dynamics of RAL DRMs for three patients who showed a switch from the N155H to the Q148H pathway.
G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not.
Abstract: Recent studies have shown that HIV-2 resistance to raltegravir involves one of three resistance mutations, N155H, Q148R/H and Y143C, previously identified as resistance determinants in the HIV-1 integrase coding sequence.
Discussion: For the G140S/Q148H pattern, Q148H caused a major catalytic defect while conferring a high level of resistance to RAL, the catalytic defect being rescued in vitro by the secondary G140S mutation, which did not itself confer resistance.
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 str
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 cost
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.
Discussion: These findings are comparable to the data obtained in a previous analysis of Q148H with N155H mutants of HIV-1.
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.
Abstract: The first had the mutations G140S+Q148H+S230N, the second had Y143R+G163R and the third had no evidence of genotypic resistance in integrase.
HIV mutation literature information.
PMID: 
2011
Journal of medical virology
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