Effects of raltegravir or elvitegravir resistance signature mutations on the barrier to dolutegravir resistance in vitro.
PMID: 25691633
2015
Antimicrobial agents and chemotherapy
Abstract: In the E92Q, Y143C, Y143R, and N155H mutants, no secondary substitutions were associated with DTG.
Abstract: One explanation for this high barrier to resistance is that no additional secondary substitution of E92Q, Y143C, Y143R, or N155H simultaneously increased the fold change in 50% effective concentration (EC50) to DTG and infectivity.
Abstract: We conducted an in vitro resistance selection study using wild-type HIV-1 and mutants with the E92Q, Y143C, Y143R, Q148H, Q148K, Q148R, and
Cross-resistance to elvitegravir and dolutegravir in 502 patients failing on raltegravir: a French national study of raltegravir-experienced HIV-1-infected patients.
PMID: 25558077
2015
The Journal of antimicrobial chemotherapy
Abstract: The most frequent mutations observed were N155H/S (19.1%), Q148G/H/K/R (15.4%) and Y143C/G/H/R/S (6.7%).
Lack of resistance to integrase inhibitors among antiretroviral-naive subjects with primary HIV-1 infection, 2007-2013.
4Method: Sequences were assembled with Sequencher (version 4.9; Gene Codes Corp, Ann Arbor, Ml) and submitted to the Stanford University HIV Drug Resistance Database (version 6.3.0; http://hivdb.stanford.edu on August 21, 2013) to identify ""major"" INSTI mutations (T66I, E92Q, G140S, Y143C/H/R, S147G, Abstract: Consensus sequencing identified no subjects with major INSTI mutations (T66I, E92Q, G140S, Y143C/H/R, S147G, Q148H/K/R, N155H).
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: None of the HIV-O viruses selected either N155H or Y143C.
2014 Update of the drug resistance mutations in HIV-1.
Discussion: Raltegravir failure is associated with integrase mutations in at least 3 distinct, but not exclusive, genetic pathways defined by 2 or more mutations including (1) a signature (major) mutation at Q148H/K/R, N155H, or Y143R/H/C; and (2) 1 or more additional minor mutations.
Discussion: The Y143R/H/C mutation is uncommon.
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 +
Abstract: In all cellular models analysed, dolutegravir showed full efficacy against N155H and Y143C mutants (dolutegravir fold-change resistance ranging from 0.1 to 1.4; raltegravir fold-change resistance ranging from 0.1 to 10.3).
HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen.
Introduction: As in HIV-1 the association T97A/Y143C does not confer resistance to DTG, extreme caution must be taken when extrapolating HIV-1 knowledge to HIV-2.
Introduction: Info
Discussion: But disparate observations have been made on this matter by different HIV-2 study groups: one group agreed with our results and reported no switch of genotypic resistance profiles in the HIV-2 IN, but another group reported the switch from the N155H to the Y143C resistance pathway by both population and clonal sequencing.
Discussion: It is known that this secondary mutation increases the level of resistance to RAL of HIV-2 mutants in a Y143C- or N155H-resistant background, playing a more important role in the HIV-2 than in the HIV-1 context.
Comparison of illumina and 454 deep sequencing in participants failing raltegravir-based antiretroviral therapy.
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-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: At failure, major RAL resistance mutations included Q148H/R/K (21/47; 45%), N155H (14/47; 30%), Y143R/H/C (3/47; 6%) and E92Q (1/47; 2%).
Resistance to HIV integrase strand transfer inhibitors among clinical specimens in the United States, 2009-2012.
Abstract: Major integrase mutations included T66AIK, E92QV, F121Y, Y143CHR, S147G, Q148HKR, and N155H; multiple accessory mutations were also assessed.
HIV mutation literature information.
PMID: 
2015
Antimicrobial agents and chemotherapy
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