MK-0536 inhibits HIV-1 integrases resistant to raltegravir.
PMID: 21876054
2011
Antimicrobial agents and chemotherapy
Abstract: It is also effective against INs that carry the three main RAL resistance mutations (Y143R, N155H, and to a lesser extent G140S-Q148H) and against the G118R mutant.
Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance.
Discussion: Generally, the amino acid changes that appear in conjunction with Q148H/K/R, N155H and Y143C/R augment the level of raltegravir resistance in HIV-1 and, in some cases, mitigate the fitness costs incurred by primary resistance-associated mutations.
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.
The HIV-1 integrase genotype strongly predicts raltegravir susceptibility but not viral fitness of primary virus isolates.
Abstract: OBJECTIVE: : Resistance to raltegravir is associated with three genetic pathways defined by the mutations Y143R/C, Q148H/R/K or N155H in integrase, which also infer a viral fitness cost.
Abstract: The first had the mutations G140S+Q148H+S230N, the second had Y143R+G163R and the third had no evidence of genotypic resistance in integrase.
Impact of Y143 HIV-1 integrase mutations on resistance to raltegravir in vitro and in vivo.
PMID: 19901095
2010
Antimicrobial agents and chemotherapy
Abstract: A molecular modeling study confirmed that Y143R/C mutations play a role similar to that determined for Q148R/H mutations.
Abstract: Furthermore, the 50% effective concentration (EC(50)) determined for Y143R/C mutants was significantly higher than that obtained with G140S/Q148R mutants.
Abstract: However, Y143R/C activity can be kinetically restored, thereby reproducing the effect of the secondary G140S mutation that rescues the defect associated with the Q148R/H mutants.
Abstract: Our observations demonstrate that Y143R/C mutants are strongly impaired for both of these activities in vitro.
Abstract: The ai
Early emergence of raltegravir resistance mutations in patients receiving HAART salvage regimens.
Abstract: In two patients with raltegravir resistance, the simultaneous appearance of additional mutations (Y143R and E170A) with an unclear impact on susceptibility to raltegravir or on integrase activity was observed.
Genotypic/phenotypic patterns of HIV-1 integrase resistance to raltegravir.
PMID: 20056687
2010
The Journal of antimicrobial chemotherapy
Abstract: Unlike mutations at position 143 (Y143S/K/R), identified alone or in combination with others, mutations at position 148 and 155 were always found in combination.
A dynamic model of HIV integrase inhibition and drug resistance.
Result: During clinical studies of raltegravir, three pathways to resistance have been observed involving residues N155H, Q148H/K/R, and Y143C/R.
Discussion: In patients failing therapy with either raltegravir or elvitegravir, the mutations Y143R/C/H have been detected, but no mutations of H67 have been observed in patients.
Discussion: Since the Y143R/G/F mutants of integrase are viable and infective, and since no mutants of H67 have yet been encountered in patients, the sum of these data suggests that H67 is more likely to play a catalytic role than Y143.
Biochemical and pharmacological analyses of HIV-1 integrase flexible loop mutants resistant to raltegravir.
Abstract: Resistance to raltegravir (RAL), the first HIV-1 integrase (IN) inhibitor approved by the FDA, involves three genetic pathways: IN mutations N155H, Q148H/R/K, and Y143H/R/C.
Natural polymorphisms of integrase among HIV type 1-infected South African patients.
PMID: 20377427
2010
AIDS research and human retroviruses
Abstract: Amino acid sequence analysis revealed there were no primary mutations (Y143R/C/H, Q148H/R/K, and N155H/S) associated with reduced susceptibility to the integrase inhibitors raltegravir and elvitegravir.
HIV-1 resistance patterns to integrase inhibitors in antiretroviral-experienced patients with virological failure on raltegravir-containing regimens.
PMID: 20388636
2010
The Journal of antimicrobial chemotherapy
Abstract: Four different patterns of IN mutations were observed: (i) emergence of Q148H/R with secondary mutations (n=5 patients); (ii) emergence of N155H, then replaced by a pattern including Y143C/H/R (n=3); (iii) selection of S230N (n=1); and (iv) no evidence of selection of IN mutations (n=2).
Abstract: The median plasma raltegravir Cmin was lower in patients with selection of the N155H mutation followed by Y143C/H/R compared with patients with Q148H/R and with patients without emerging mutations or without VF.
Abstract: The median raltegravir and elvitegravir fold changes (FCs) were 244 (154-647) and 793 (339-892), respectively,
HIV mutation literature information.
PMID: 
2011
Antimicrobial agents and chemotherapy
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