Abstract: To study this at a biochemical level, purified recombinant SIVmac239 wild-type (WT) and E92Q, T97A, G118R, Y143R, Q148R, N155H, R263K, E92Q T97A, E92Q Y143R, R263K H51Y, and G140S Q148R recombinant substitution-containing IN enzymes were produced, and each of the characteristics strand transfer, 3'-processing activity, and INSTI inhibitory constants was assessed in cell-free as
Lack of integrase inhibitors associated resistance mutations among HIV-1C isolates.
PMID: 26626277
2015
Journal of translational medicine
Discussion: This includes T66IAK, E92Q, F121Y, G140SA, Y143HCR, Q146P, S147G, Q148KHR, and N155HS; (2) minor INI-resistance mutations were defined as non-polymorphic or minimally polymorphic mutations that reduce INI susceptibility H51Y, L74 M, T97A, E138AK, S153Y,
Dolutegravir maintains a durable effect against HIV replication in tissue culture even after drug washout.
PMID: 26142476
2015
The Journal of antimicrobial chemotherapy
Abstract: In addition, we assessed the role of the R263K substitution within the integrase ORF that is associated with low-level resistance to dolutegravir.
Abstract: The R263K substitution did not significantly impact on levels of RT activity after drug washout, suggesting that dolutegravir remained tightly bound to the integrase enzyme despite the presence of this mutation.
Resistance mutations against dolutegravir in HIV integrase impair the emergence of resistance against reverse transcriptase inhibitors.
Abstract: DESIGN AND METHODS: We tested the ability of DTG-resistant viruses containing either the R263K or G118R and/or H51Y mutations to develop further resistance against several reverse transcriptase inhibitors during in-vitro selection experiments.
Abstract: Now, we sought to investigate the facility with which resistance on the part of R263K-containing viruses might develop.
Abstract: The R263K integrase resistance mutation was observed in two of these individuals who received suboptimal background regimens.
Abstract: We have previously selected mutations at position R263K, G118R, H51Y, and S153F plus R263K combination of integrase mutations in the proviral DNA of one individual successfully treated with dolutegravir.
Introduction: As such, tissue culture selection studies with this drug have revealed the emergence of the R263K mutation in the integrase of HIV subtypes B and circulating recombinant form CRF02_A/G viruses .
Introduction: Here, we present the biochemical characterization of the M50I substitution alone and in combination with the primary resistance mutation R263K in subtype B integrase.
Introduction: However, the R263K mutation has been found in INSTI-naive ART-experienced patients receiving DTG treatment who have failed therapy with this drug .
Introduction: In addition, this polymorphism has been observed in combination with R263K in a patient who subsequently failed treatment with RAL .|mgd
HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen.
Introduction: Corroborating this is the fact that, at this time, it is still unknown whether the combination H51Y/R263K, that confers some level of resistance to DTG in HIV-1, could be relevant as a mutational pathway leading to HIV-2 resistance.
Progressive emergence of an S153F plus R263K combination of integrase mutations in the proviral DNA of one individual successfully treated with dolutegravir.
PMID: 24917583
2014
The Journal of antimicrobial chemotherapy
Abstract: CONCLUSIONS: The E138K substitution failed to restore the defect in viral replication capacity that is associated with R263K, confirming previous selection studies that failed to identify compensatory mutation(s) for the latter primary mutation.
Abstract: METHODS: We used biochemical cell-free strand-transfer assays and tissue culture assays to characterize the effects of the E138K/R263K combination of mutations on resistance to dolutegravir, integrase enzyme activity and HIV-1 replication capacity.
Abstract: RESULTS: We show here that the addition of the E138K substitution to R263K increased the resistance of HIV-1 to dolutegravir but failed to restore viral replication capacity, integrase str
Fitness impaired drug resistant HIV-1 is not compromised in cell-to-cell transmission or establishment of and reactivation from latency.
Abstract: Here, we have studied the impact of R263K on HIV replication capacity and the ability of HIV to establish or be reactivated from latency and/or spread through cell-to-cell transmission.
Abstract: The clinical use of a novel integrase inhibitor, dolutegravir (DTG), has established hope that this compound may limit HIV persistence, since no treatment-naive patient treated with DTG has yet developed resistance against this drug, even though a R263K substitution in integrase confers low-level resistance to this drug in tissue culture.
Introduction: Altogether, these observations suggest that R263K may represent an evolutionary dead-end that could explain the scarcity of virological failures and resistance mutations in individuals treated with DTG.
Introduction: Further studies have shown that se
Progressive emergence of an S153F plus R263K combination of integrase mutations in the proviral DNA of one individual successfully treated with dolutegravir.
PMID: 25394027
2014
Journal of the International AIDS Society
Abstract: CONCLUSIONS: Secondary mutations to R263K following selection with DTG have all led to diminished viral and enzymatic fitness, helping to explain why resistance to DTG in previously drug-naive subjects has never been observed.
Abstract: Conversely, combinations of R263K together with multiple resistance mutations for RAL and/or EVG at positions 92,143, 148 and 155 resulted in even further diminished enzymatic activity that may be incompatible with viral survival.
Abstract: In contrast, a R263K mutation that confers low-level resistance (3-4 fold) to DTG has been selected by DTG in culture.
Abstract: Modelling of the 3-dimensional structure of integrase suggests that R263K is located in a region that may not permit further mutagenesis if secondary mutations at H51Y
HIV-1 group O integrase displays lower susceptibility to raltegravir and has a different mutational pathway for resistance than HIV-1 group M.
PMID: 25397483
2014
Journal of the International AIDS Society
Abstract: Mutations selected in HIV-O can be classified as follows: (1) mutations described for HIV-M such as T97A, Q148R, V151A/I (RAL), T66I, E92Q, E157Q (EVG) and M50I, R263K (DTG) and (2) signature mutations for HIV-O.
Abstract: Only the HIV-O/Div selected the Q148R mutation for RAL and R263K+M50I for DTG, as previously described for HIV-M.
HIV mutation literature information.
PMID: 
2015
Journal of virology
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