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.
Abstract: Characterization of the phenotypic evolution showed that the switch from N155H to Y143C/R was linked to an increase in resistance to RAL.
Abstract: The emergence of the N155H mutation was replaced by a pattern including the Y143R/C/H mutations in three patients with anti-HIV treatment failure.
Result: In all three patients, the initial selection of the N155H mutation was followed by its disappearance and replacement by a pattern comprising the Y143H/R/C mutations with other mutations (T97A in 3 patients, L74M in 2 patients and G163R and S230R in one patient each); RAL was stopped between months 6
Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness.
PMID: 20634701
2010
Journal of acquired immune deficiency syndromes (1999)
Discussion: As expected, the mutant viruses were fitter than wild-type in the presence of drug, with the N155H mutant being more fit than the Q148H mutant.
Discussion: Clones with G140S/Q148H showed higher integrase-mediated replication capacity as compared to clones with Q148R or N155H alone; the G140S/Q148H clones also exhibited higher levels of raltegravir resistance.
Discussion: However, the G140S/Q148H double-mutant was fitter than the E92Q/N155H double mutant.
Discussion: In that study, the appearance of viruses w
HIV-1 subtype B and C integrase enzymes exhibit differential patterns of resistance to integrase inhibitors in biochemical assays.
Abstract: CONCLUSION: Polymorphic differences within the subtype B and C integrase genes likely cause variations in the contribution of N155H alone or in combination with E92Q to drug resistance.
Abstract: METHODS: We compared the susceptibility of subtype B and C HIV-1 integrase enzymes, harboring the previously reported resistance mutations E92Q, N155H, and E92Q/N155H, to clinically relevant integrase inhibitors.
Abstract: RESULTS: Subtype C integrase enzymes bearing the resistance mutations E92Q/N155H were approximately 10-fold more susceptible to each of two
Discovery of potent HIV integrase inhibitors active against raltegravir resistant viruses.
Abstract: Several compounds with excellent activities against wild-type virus as well as against the viruses with the mutations Q148H/G140S or N155H/E92Q were reported.
Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors.
Abstract: Notably, MK-2048 is equally potent against wild-type IN and raltegravir-resistant IN mutant N155H, suggesting this inhibitor may bind similarly within their drug-binding pockets.
Abstract: Studies of raltegravir-resistant IN mutants N155H and Q148H without inhibitors demonstrated that their capacity to assemble the synaptic complex and promote concerted integration was similar to their reported virus replication capacities.
Abstract: The concerted integration activity of Q148H showed a higher cross-resistance to raltegravir than observed with N155H, providing evidence as to why the Q148H pathway with secondary mutations is the predominant pathway upon prolong
In-vitro phenotypic susceptibility of HIV-2 clinical isolates to the integrase inhibitor S/GSK1349572.
Abstract: We found a seven-, 13- and 18-fold increase in EC50 values to S/GSK1349572 for the HIV-2 double (T97A + Y143C; G140S + Q148R) and triple (G140T + Q148R + N155H) mutants, respectively, obtained from two raltegravir-experienced patients.
Dynamic escape of pre-existing raltegravir-resistant HIV-1 from raltegravir selection pressure.
Abstract: Double 148R+N155H mutants were also detected in 1.7% of viruses at virological failure in association with E138K and/or G163R.
Abstract: Using quantitative deep HIV-1 sequencing in a subject who developed virological failure to deep salvage therapy with raltegravir, we found that most Q148R and N155H mutants detected at the time of virological failure originated from pre-existing minority Q148R and N155H variants through independent evolutionary clusters.
Molecular mechanisms of retroviral integrase inhibition and the evolution of viral resistance.
Abstract: We show that like the Q148H/G140S and N155H HIV-1 IN variants, the analogous S217H and N224H PFV INs display reduced sensitivity to raltegravir in vitro.
Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir.
Abstract: The N155 H INI resistance-associated mutation (RAM) was detected in the virus population from one ARV-treated, INI-naive patient, and the 72I and 201I polymorphisms were detected in samples from 36 and 38 patients respectively.
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
HIV mutation literature information.
PMID: 
2010
Virology
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