The use of integrase inhibitors in treatment-experienced patients.
PMID: 19959414
2009
European journal of medical research
Introduction: A genotypic resistance test could be performed in 38 of these patients of whom 35 selected resistance mutations in the integrase gene following the N155H or the Q148H/R/K path almost always associated with one additional mutation.
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.
Introduction: The N155H or the Q148H/R/K alone are associated with high or intermediate levels of resistance that beca
HIV resistance to raltegravir.
PMID: 19959417
2009
European journal of medical research
Abstract: HIV resistance to raltegravir is the consequence of mutations located close to the integrase active site, which can be divided into three main evolutionary pathways: the N155H, the Q148R/H/K and the Y143R/C pathways.
Abstract: Resistance is frequently initiated by viruses carrying mutations of the N155H pathway, followed by emergence and further dominance of viral genomes carrying mutations of the Q148R/H/K or of the Y143R/C pathways, which express higher levels of resistance.
Biochemical analysis of HIV-1 integrase variants resistant to strand transfer inhibitors.
PMID: 18577511
2008
The Journal of biological chemistry
Abstract: In the case of the Q148R variant, the origin of reduced compound affinity lies in alterations to the active site that reduce the binding of a catalytically essential magnesium ion.
Abstract: The Q148R variant was the most defective enzyme.
Analysis of natural sequence variation and covariation in human immunodeficiency virus type 1 integrase.
Abstract: The critical mutations that determine the resistance pathways to raltegravir and elvitegravir (N155H, Q148K/R/H, and E92Q) were either rare or absent from the 1,165-sequence data set.
Selection of diverse and clinically relevant integrase inhibitor-resistant human immunodeficiency virus type 1 mutants.
Abstract: Q148R/K and N155H, which were found in patients failing raltegravir treatment in Phase IIb studies, were observed during passage with raltegravir with this method.
Abstract: Q148R and F121Y were the two main pathways of resistance to S/GSK-364735.
Drug resistance profiles for the HIV integrase gene in patients failing raltegravir salvage therapy.
Abstract: Clonal analysis showed the coexistence, in patient 1, of the two common resistance pathways (mutations Q148R/H and N155H) found in distinct quasi-species.
Abstract: RESULTS: At the time of VF, RAL-resistance mutations were selected: (i) Q148R in patients 1 and 3; (ii) T66A and E92Q in patient 2.
Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors.
Result: Among the CCD mutations shown to directly reduce raltegravir or elvitegravir susceptibility - H51Y, T66I, E92Q, F121Y,
Discussion: Nearly all INI-resistance mutations known to directly reduce HIV-1 susceptibility were nonpolymorphic including H51Y, T66I, E92Q, F121Y, G140S, Y143C/H/R, Q146P, S147G, Q148H/R/K, S153Y, N155H/S, and R263K.
Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants.
Introduction: For raltegravir the two main mutations are N155H or Q148H/R/K with 10- and 25-fold in vivo resistance, respectively.
Resistance mutations in human immunodeficiency virus type 1 integrase selected with elvitegravir confer reduced susceptibility to a wide range of integrase inhibitors.
Abstract: We find the primary resistance-conferring mutations to be Q148R, E92Q, and T66I and demonstrate that they confer a reduction in susceptibility not only to elvitegravir but also to raltegravir (MK-0518) and other integrase inhibitors.
Clade-specific HIV-1 integrase polymorphisms do not reduce raltegravir and elvitegravir phenotypic susceptibility.
Abstract: Control Q148R mutant virus showed fold change values of 17.85 +/- 2.77 and 88.94 +/- 9.02 for raltegravir and elvitegravir, respectively, whereas the average fold change for the clinical samples was 0.91 +/- 0.40, and 0.84 +/- 0.37.
HIV mutation literature information.
PMID: 
2009
European journal of medical research
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