Impact of resistance mutations on inhibitor binding to HIV-1 integrase.
PMID: 24205814
2013
Journal of chemical information and modeling
Abstract: However, mutants have emerged, such as E92Q/N155H and G140S/Q148H, which confer resistance to raltegravir (RAL), the first IN strand transfer inhibitor (INSTI) approved by the FDA, and to the recently approved elvitegravir (EVG).
Plasma raltegravir exposure influences the antiviral activity and selection of resistance mutations.
PMID: 21457126
2012
AIDS research and human retroviruses
Abstract: Integrase sequences could be obtained for 89 (84%), of whom 30 (33.7%) depicted primary RAL resistance mutations (15 N155H, eight Q148H/R, three Y143R, one E92Q, and three more than one of them).
Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens.
Figure: Panels B and D show representative dose-response data for WT, Q148R, and G140S+Q148R versus raltegravir and WT, N155H, and E92Q+N155H versus elvitegravir, respectively.
Discussion: Finally, the combination of E92Q+N155H produces robust resistance to both raltegravir and elvitegravir in HIV-2, providing a third pathway to high-level resistance.
Discussion: In contrast, the Y143C change had little or no effect on raltegravir susceptibility; robust resistance to the drug required the addition of E92Q together with
"Prolonged and substantial discordance in prevalence of raltegravir-resistant HIV-1 in plasma versus PBMC samples revealed by 454 ""deep"" sequencing."
Introduction: E92Q is also associated with another integrase-inhibitor, elvitegravir.
Introduction: Well-characterized mutations in the HIV-1 int region that confer high levels of resistance to raltegravir include E92Q, Y143R/H/C, Q148H/K/R and N155H.
Method: Primary raltegravir-associated DRMs were defined to be E92Q, Y143R/C/H, Q148H/R/K, and N155H/S (HXB2 int amino acid coordinates), according to the International AIDS Society guidelines.
Table: E92Q
HIV-1 integrase resistance among antiretroviral treatment naive and experienced patients from Northwestern Poland.
Abstract: Among 12 (26.1%) raltegravir treated patients treatment failure was observed; major InI drug resistance mutations (G140S, Q148H and N155H, V151I, E92EQ, V151I, G163R) were noted in four of these cases (8.3% of the total InI-treated patients).
Result: Development of drug resistance mutations followed two patterns: major N155H with or without subsequent accessory V151I, E92EQ, V151I, G163R mutants (three cases) and Q148H accompanied by 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%).
Resistance associated mutations to dolutegravir (S/GSK1349572) in HIV-infected patients--impact of HIV subtypes and prior raltegravir experience.
Abstract: T124A was more frequent in INI-naive patients but E92Q and Q148H/R were only seen in raltegravir-experienced individuals.
Abstract: E92Q and Q148H/R were only seen in raltegravir-experienced patients and exclusively infected with subtype B (1.9% vs. 0%, p=0.026, for E92Q and 12.6% vs. 0%, p<0.001, for Q148H/R).
Switching between raltegravir resistance pathways analyzed by deep sequencing.
Result: We also detected T97A, an accessory mutation for Y143R, and L74M and E92Q, accessory mutations for N155H, from the forward read sets (data not shown).
G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not.
Method: Single (E92Q, T97A, G140S, Q148R, Y143C, N155H) and double (G140S/Q148R, Y143C/N155H, E92Q/Y143C and T97A/Y143C) mutations were introduced into the HIV-2 wild-type N1 sequence by mutagenesis using the QuickChange II site-directed mutagenesis kit (Agilent Technologies, Santa Clara, USA) according to the manufacturer instructions.
Result: Biochemical studies have demonstrated that Q148R, N155H and Y1
Long-lasting persistence of integrase resistance mutations in HIV-2-infected patients after raltegravir withdrawal.
Abstract: RESULTS: At the time of RAL withdrawal, virus exhibited different integrase resistance pathways: G140S/Q148R, E92Q/N155H, T97A/N155H and T97A/Y143C.
Abstract: Regarding patient 2, the double-mutant E92Q/N155H was still present at M2 and M8 after stopping RAL, and was no longer detected at M12.
HIV mutation literature information.
PMID: 
2013
Journal of chemical information and modeling
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