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: 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.
Early emergence of raltegravir resistance mutations in patients receiving HAART salvage regimens.
Abstract: Mutations at positions involved in raltegravir resistance (E92G, G140S, Q148H, and N155H) were detected in 4 of 11 (36.3%) patients as early as 1 month after initiating salvage HAART.
Genotypic/phenotypic patterns of HIV-1 integrase resistance to raltegravir.
PMID: 20056687
2010
The Journal of antimicrobial chemotherapy
Abstract: DISCUSSION: Two patterns of viral evolution were observed in the resistant viral populations, driving the variants towards a fast (most of them with G140S + Q148H mutations) or progressive increase in resistance to raltegravir.
A dynamic model of HIV integrase inhibition and drug resistance.
Abstract: These models have allowed us to (1) explore the effects of key drug resistance mutations on the dynamic flexibility and conformational preferences of HIV integrase and to (2) study raltegravir binding in the context of these dynamic models of both wild type and the G140S/Q148H drug-resistant enzyme.
Introduction: Although it is a very new anti-HIV drug, raltegravir-resistant mutants of HIV integrase, such as E92Q/N155H and G140S/Q148H in the catalytic core domain, have already been identified in patients.
Introduction: This protocol was used to create dynamic models of the wild type, E92Q/N155H, and PMID: 20160635
2010
AIDS (London, England)
Abstract: Allele-specific real-time PCR (AS-PCR) systems, developed for Q148H, Q148R and N155H mutations, were performed at baseline for antiretroviral-experienced patients.
Abstract: In antiretroviral-experienced patients, Q148R minority variants were frequently detected (26/32 patients, 81%) at low-level frequency (median = 0.40%), whereas no minority variants exhibiting Q148H or N155H mutation were found.
Abstract: RESULTS: The limits of detection of AS-PCR systems were 0.10, 0.10 and 0.05% for Q148H, Q148R and N155H mutations, respectively.
Biochemical and pharmacological analyses of HIV-1 integrase flexible loop mutants resistant to raltegravir.
Abstract: By examining systematically all of the double mutants at the 140 and 148 positions, we demonstrate that only the combination G140S + Q148H is able to restore the catalytic properties of IN.
Abstract: Clinical and virological data indicate the high relevance of the combination G140S + Q148H because of its limited impact on HIV replication and very high resistance to RAL.
Abstract: Finally, we show that the G140S-Q148H double mutant exhibits the highest resistance to RAL.
Abstract: Resistance to raltegravir (RAL), the first HIV-1 integrase (IN) inhibitor approved by the FDA, involves three genetic pathways: IN mutati
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,
Primary mutations selected in vitro with raltegravir confer large fold changes in susceptibility to first-generation integrase inhibitors, but minor fold changes to inhibitors with second-generation resistance profiles.
Method: We followed-up the 50 mutations of resistance present at 32 positions: associated with in vitro or in vivo resistance to HIV-1 integrase inhibitors: H51Y, T66I/A/K, V72I, L74I/A/M, E92Q, T97A, T112I, F121Y, T125K, A128T, E138 K/A/D, G140R/C/H, Y143C/H/R, Q146K/P, S147G, Q148K/R/H, V151I,
ViMRT
HIV mutation literature information.
PMID: 
2010
Antimicrobial agents and chemotherapy
