Discussion: Cross-resistance studies with raltegravir- and elvitegravir-resistant viruses indicate that Q148H and G140S in combination with mutations L74I/M, E92Q, T97A, E138A/K, G140A, or N155H are associated with 5-fold to 20-fold reduced dolutegravir susceptibility and reduced virologic suppression in patients.
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
Method: The double mutant G140A + Q148K was made by using the Q148K mutant and the appropriate oligonucleotide to introduce the second mutation, G140A.
Method: The following sense with cognate antisense (not shown) oligonucleotides (Integrated DNA Technologies, Coralville, IA) was used in the mutagenesis: G118R, 5'-GTACATACAGACAATCGCAGCAATTTCACCAGTAC-3'; E138K, 5'-GGCGGGGATCAAGCAGAAATTTGGCATTCCCTA-3'; G140A, 5'-GGGGATCAAGCAGGAATTTGCCATTCCCTACAATC-3'; G140S, 5'-GGGGATCAAGCAGGAATTTAGCATTCCCTACAATC-3'; Y143R, 5'-GCAGGAATTTGGCATTCCCCGCAATCCCCAAAGTCAAGGA-3'; Q148H, 5'-CATTCCCTACAATCCCCAAAGTCATGGAGTAATAGAATCTA-3'; Q148K
Reduced HIV-1 integrase flexibility as a mechanism for raltegravir resistance.
Abstract: Obtaining crystallographic structure information on the Q148H/R, G140S/A primary and secondary mutations has been elusive.
"Prolonged and substantial discordance in prevalence of raltegravir-resistant HIV-1 in plasma versus PBMC samples revealed by 454 ""deep"" sequencing."
Method: Secondary raltegravir-associated DRMs were defined to be E92V, Q95K, T97A, F121Y, E138A/K, G140A/C/S, S147G, V151A/I/L, M154I/L, E157Q, and G163K/R, and linkages examined were T97A and Y143C/R, E138A/K and Q148H/K/R, G140S and Q148H/K/R, and G163K/R and
Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance.
Discussion: Studies of HIV-1 patients have identified three principal mutational patterns that emerge in response to raltegravir treatment: Q148H/K/R with or without G140S/A, N155H with or without E92Q and Y143C/R with or without T97A.
G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not.
Result: All group A viruses harbored a Q148R resistance mutation, associated with G140S in two cases (patients T3 and T4) and G140A in two others (patients T5 and T7; Table 2).
Result: Biochemical studies have demonstrated that Q148R, N155H and Y143C are primary resistance mutations giving rise to HIV-1 resistance whereas G140S/A and E92Q are secondary resistance mutations increasing resistance and viral fitness.
Subtype diversity associated with the development of HIV-1 resistance to integrase inhibitors.
Abstract: Thirteen patients failed raltegravir (RAL)-containing regimens within 8 +- 1 months, in association with the major Q148K/R/H and G140A/S (n = 8/24) or N155H (n = 5/24) mutational pathways.
Genetic variation of the HIV-1 integrase region in newly diagnosed anti-retroviral drug-naive patients with HIV/AIDS in Korea.
PMID: 20946407
2011
Clinical microbiology and infection
Abstract: Major mutation sites in the integrase (E92Q, F121Y, G140A/S, Y143C/R, Q148H/R/K and N155H) were not detected, and only a few minor mutation sites (L74M, V151I, E157Q, V165I, I203M, S230N and D232N) were identified in 21 strains (28%).
Extended use of raltegravir in the treatment of HIV-1 infection: optimizing therapy.
HIV mutation literature information.
PMID: 
2014
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