Abstract: The emergence of the N155H mutation was replaced by a pattern including the Y143R/C/H mutations in three patients with anti-HIV treatment failure.
Introduction: In a previous work, we reported how patients who had failed to respond to therapies under RAL-containing regimens presented the N155H mutation, which was then replaced over time by the Y143C/H/R mutations.
Introduction: The most frequent primary RAL resistance mutations emerging in vivo at virological failure (VF) in the IN gene are Q148H/R/K, N155H, and to a lesser extent Y143C/H/R.
Result: In all three patients, the initial selection of the N155H
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,
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.
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.
A dynamic model of HIV integrase inhibition and drug resistance.
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.
Characterization and structural analysis of HIV-1 integrase conservation.
Abstract: Mutations Q148R (2 months) followed by G140A/Q148R and then G140A/Y143CHR/Q148R/G163R were detected in the virus from one patient, and these reverted to wild type when treatment was withdrawn, although clonal analysis identified maintenance of RAL resistance minority species at this time point.
Effects of HIV type-1 immune selection on susceptability to integrase inhibitor resistance.
Result: Of the 38 major and minor integrase inhibitor resistance associated codons, 44, 61, 66, 92, 121, 140, 143, 147, 148, 155, 226 and 263 were the only positions absolutely conserved across all 342 sequences and these included six primary resistance-associated mutations for raltegravir and elvitegravir (T66I, E92Q, G140S, Y143C/H/R Q148H/R/K and N155S/H).
Discussion: In this population-based review of all sites associated with integrase inhibitor resistance in 342 natural isolates of HIV-1 obtained from two geographically distinct cohorts in Switzerland and Australia, we observed that the primary raltegravir and elvitegravir resistance mutations T66
The use of integrase inhibitors in treatment-experienced patients.
PMID: 19959414
2009
European journal of medical research
Abstract: Tolerance was remarkably good and virological failure was often associated with selection of integrase gene resistance mutations following the Y143C/H/R, Q148H/K/R o less frequently the NI55H paths.
Introduction: Overall, by week 96 resistance tests were available for 112 raltegravir treated patients of whom 73% had integrase mutations at one of the three positions (Y143C/H/R, Q148H/K/R N155H) almost always in combination with at least one other mutation.
Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors.
Result: Y143H was present in three subtype C isolates and one subtype D isolate.
Result: Among the CCD mutations shown to directly reduce raltegravir or elvitegravir susceptibility - H51Y, T66I, E92Q, F121Y, G140S, Y143C/H/R, Q146P, S147G, Q148H/R/K, S153Y, N155H/S, and E157Q - only positions 153 and 157 are polymorphic (prevalence >= 0.5%) with S153A and E157Q each present in 1% of sequences (Figures 1).
HIV mutation literature information.
PMID: 
2010
PloS one
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