Use of dolutegravir in two INI-experienced patients with multiclass resistance resulted in excellent virological and immunological responses.
PMID: 25397500
2014
Journal of the International AIDS Society
Abstract: Ultra-deep sequencing of integrase showed the selection of Q148R, E138K+Q148K, and N155H variants and phenotypic raltegravir resistance was demonstrated.
Abstract: Ultra-deep sequencing showed selection of N155H, followed by Q95K and V151I variants and phenotypic raltegravir resistance was demonstrated.
Table: N155H
Longitudinal analysis of integrase N155H variants in heavily treated patients failing raltegravir-based regimens.
Abstract: Because the emergence of RAL resistance is usually initiated by the N155H mutant, we assessed the role of minor N155H-mutated variants in circulating RNA and archived DNA in five heavily treated patients experiencing long-term RAL therapy failure and harbouring three different resistance profiles determined by standard genotyping.
Abstract: CONCLUSIONS: The N155H mutation present at various levels from minority to majority showed no relationship with the three RAL-associated resistance profiles, suggesting that this mutant may not play a role in determining different resistance profiles.
Abstract: During RAL failure, the mutation N155H was detected at different levels in three patients displaying the N155H pathway and gradually declined when the double mutant Q148H
Activities, crystal structures, and molecular dynamics of dihydro-1H-isoindole derivatives, inhibitors of HIV-1 integrase.
Introduction: Using a panel of recombinant INs that carry the Y143R, N155H and G140S-Q148H mutations, we reported that elvitegravir (EVG, Gilead Sciences), dolutegravir (DTG, ViiV Healthcare/Shionogi) and MK-0536 (Merck & Co.) retain high efficacy against these RAL-resistant mutants.
Result: However, both conformations predicted modest (2- to 8-fold) increases in IC50 against the Y143R and N155H mutants and a greater increase (15- to 225-fold) against the G140S-Q148H mutant.
Result: In contrast, the N155H mutation causes a 10-fold reduction in susceptibility to RAL.
Result: In the context of the
Impact of primary elvitegravir resistance-associated mutations in HIV-1 integrase on drug susceptibility and viral replication fitness.
PMID: 23529738
2013
Antimicrobial agents and chemotherapy
Abstract: Primary INSTI resistance-associated mutations (RAMs) at six IN positions have been identified in HIV-1-infected patients failing EVG-containing regimens in clinical studies: T66I/A/K, E92Q/G, T97A, S147G, Q148R/H/K, and N155H.
Abstract: Recombinant viruses containing the six most common mutations exhibited a range of reduced EVG susceptibility: 92-fold for Q148R, 30-fold for N155H, 26-fold for E92Q, 10-fold for T66I, 4-fold for S147G, and 2-fold for
Binding mode prediction of biologically active compounds from plant Salvia Miltiorrhiza as integrase inhibitor.
Introduction: Binding orientations and favorable interactions of ligands against the wild-type (WT) and three different mutation strains; Y212R (equivalent to Y143R
Discussion: Our docking analysis suggested that M532 might be active against the mutation of N224H IN (corresponding to N155H HIV-1 IN).
Discussion: The hypothetically predicted mode of action of these two compounds against the Y212R (corresponding to Y143R HIV-1 IN) and N224H (corresponding to N155H HIV-1 IN) PFV IN are displayed in (Figures 3B & 3C), respectively.
In vitro phenotypes to elvitegravir and dolutegravir in primary macrophages and lymphocytes of clonal recombinant viral variants selected in patients failing raltegravir.
PMID: 23798668
2013
The Journal of antimicrobial chemotherapy
Abstract: No variations were observed for the Y143R/C (+/-T97A) or N155H variants.
Origin of minority drug-resistant HIV-1 variants in primary HIV-1 infection.
PMID: 23847055
2013
The Journal of infectious diseases
Abstract: Second, prevalence between MVs harboring the frequent mutation M184V and the particularly uncommon integrase mutation N155H differed highly significantly in acute or recent seroconverters (8.2% vs 0.5%; P < .001).
Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics.
Abstract: Signature HIV-1 integrase mutations associated with clinical raltegravir resistance involve 1 of 3 primary genetic pathways, Y143C/R, Q148H/K/R and N155H, the latter 2 of which confer cross-resistance to elvitegravir.
Result: A single conformation for the terminal 3' adenylate of the Q148H/G140S and N155H IN-DNA complexes was modeled with the nucleobase pi-stacked against DTG's metal-chelating scaffold (Figures 4A and 4B, respectively).
Result: For instance, the distance between the Calpha atoms of D64 and N155H was increased by roughly 0.5 A compared with wild-type IN
Impact of resistance mutations on inhibitor binding to HIV-1 integrase.
PMID: 24205814
2013
Journal of chemical information and modeling
Abstract: However, mutants have emerged, such as E92Q/N155H and G140S/Q148H, which confer resistance to raltegravir (RAL), the first IN strand transfer inhibitor (INSTI) approved by the FDA, and to the recently approved elvitegravir (EVG).
Molecular dynamics approaches estimate the binding energy of HIV-1 integrase inhibitors and correlate with in vitro activity.
PMID: 22037850
2012
Antimicrobial agents and chemotherapy
Abstract: Four well-characterized compounds (raltegravir, elvitegravir, MK-0536, and dolutegravir) were used as a training set, and the data for their in vitro activity against the Y143R, N155H, and G140S/Q148H mutants were used in addition to the wild-type (WT) IN data.
HIV mutation literature information.
PMID: 
2014
Journal of the International AIDS Society
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