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 HIV mutation literature information.


  Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades.
 PMID: 26311843       2015       The Journal of antimicrobial chemotherapy
Abstract: Among raltegravir recipients with viraemia (median 3523 HIV-1 RNA copies/mL), 113/255 (44.3%) had one or more major INI RAMs, most commonly N155H (45/255, 17.6%), Q148H/R/K + G140S/A (35/255, 13.7%) and Y143R/C/H (12/255, 4.7%).
Abstract: Comparing subtype B with non-B clades, Q148H/R/K occurred in 42/209 (20.1%) versus 2/46 (4.3%) subjects (P = 0.009) and G140S/A occurred in 36/209 (17.2%) versus 1/46 (2.2%) subjects (P = 0.005).
Abstract: Reduced occurrence of Q148H/R/K + G140S/A was seen in non-B clades versus subtype B, and was explained by the higher genetic barrier to the


  Characterization of the Drug Resistance Profiles of Integrase Strand Transfer Inhibitors in Simian Immunodeficiency Virus SIVmac239.
 PMID: 26378179       2015       Journal of virology
Abstract: Both viruses and enzymes containing Q148R and G140S Q148R showed moderate levels of resistance against DTG.
Abstract: RAL and EVG showed reduced activity against both viruses and against enzymes containing Q148R, E92Q Y143R, and G140S Q148R.
Abstract: The results show that the G118R and G140S Q148R substitutions decreased Km' and Vmax'/Km' for strand transfer compared to those of the WT.


  Design, Synthesis, and Biological Evaluation of 1,2-Dihydroisoquinolines as HIV-1 Integrase Inhibitors.
 PMID: 26487913       2015       ACS medicinal chemistry letters
Abstract: Interestingly, these compounds showed similar ST inhibitory activity in G140S mutant, suggesting they can act against resistant strains.


  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,


  HIV-1-infected patients with advanced disease failing a raltegravir-containing salvage regimen in Sao Paulo, Brazil.
 PMID: 24359837       2014       International journal of antimicrobial agents
Abstract: Most samples with Q148H/R/K also showed G140S/A/C (21/47; 45%).


  Bicyclic 1-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxamide-containing HIV-1 integrase inhibitors having high antiviral potency against cells harboring raltegravir-resistant integrase mutants.
 PMID: 24471816       2014       Journal of medicinal chemistry
Abstract: Importantly, some of these new inhibitors retain greater antiviral efficacy compared to that of RAL when tested against a panel of IN mutants that included Y143R, N155H, G140S/Q148H, G118R, and E138K/Q148K.
Conclusion: Several compounds have selectivity indices of greater than 20,000, and certain of these inhibitors have greater antiviral efficacies than RAL against a panel of IN mutants that included Y143R, N155H, G118R, and the double mutants G140S/Q148H and E1


  Comparison of illumina and 454 deep sequencing in participants failing raltegravir-based antiretroviral therapy.
 PMID: 24603872       2014       PloS one
Method: Patients with more than one darunavir resistance-associated mutation or with known major integrase resistance-associated mutations (N155H, Q148H/R/K, Y143C/R, and G140S) were excluded from the study.


  HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen.
 PMID: 24681625       2014       PloS one
Introduction: Information on its efficiency against HIV-2 strains bearing integrase inhibitor resistance mutations is still limited, but phenotypic assays carried out with HIV-2 clinical isolates from patients treated with RAL showed that mutations T97A/Y143C, G140S/Q148R or G140T/Q148R/N155H conferred moderate resistance to DTG (7-18-fold increase of the EC50).
Introduction: Overall, three major resistance
Discussion: Mutation G140S, usually selected with Q148R to mitigate the fitness costs incurred by this primary mutation, was not observed in our study, probably due to the short exposure time of the patient to RAL (only 5 months).


  Comparative replication capacity of raltegravir-resistant strains and antiviral activity of the new-generation integrase inhibitor dolutegravir in human primary macrophages and lymphocytes.
 PMID: 24860155       2014       The Journal of antimicrobial chemotherapy
Abstract: In C8166 (the only cell model in which replication capacity was sufficient to perform the test) dolutegravir showed full efficacy against mutations N155H + Y143C (dolutegravir fold-change resistance: 0.6) and a slightly lower activity against G140S+Q148H (dolutegravir fold-change resistance: 2.1).
Abstract: In MDMs and PBMCs, a dramatic decrease in viral replication was observed for the double mutants N155H + Y143C and G140S + Q148H (ranging from 0.1% to 2.5% compared with wild-type).
Abstract: The following raltegravir resistance mutations were analysed: N155H, Y143C, N155H +  PMID: 24899199       2014       Journal of virology
Abstract: Conversely, RT-E138K and -Y181C mutations improved the fitness of the IN-G140S/Q148H mutant virus in the presence of raltegravir (RAL); the RT-K103N mutation had no effect.
Abstract: However, both the RT-K103N plus IN-G140S/Q148H and the RT-E138K plus IN-G140S/Q148H mutant viruses had significantly greater fold increases in 50% inhibitory concentrati



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