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.
Long-lasting persistence of integrase resistance mutations in HIV-2-infected patients after raltegravir withdrawal.
Abstract: In patient 3, RAL-resistant virus with T97A/N155H mutations were still present 1 month after stopping RAL, and were no longer detected at M14.
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.
Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance.
Abstract: Amino acid changes Q148R and N155H individually conferred resistance to raltegravir (14-fold and seven-fold, respectively), whereas the Y143C replacement had no statistically significant effect on raltegravir sensitivity.
Abstract: CONCLUSION: Our data support clinical studies of raltegravir for treating HIV-2 infection and show that the Q148R and N155H changes alone are sufficient for raltegravir resistance in HIV-2.
Abstract: The combination of Q148R with N155H resulted in high-level raltegravir resistance (>1000-fold).
Discussion: 2) and that the Q148R and N155H changes individually confer moderate r
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.
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.
A dynamic model of HIV integrase inhibition and drug resistance.
Discussion: E92Q is linked with N155H to make a double mutant that is far more raltegravir-resistant than either single mutant.
Discussion: But the two binding modes that raltegravir is predicted to display against the wild type appear to explain why the E92Q/N155H double mutant is highly raltegravir-resistant.
Discussion: If the current preliminary hypothesis of the mechanism of drug resistance for the E92Q/N155H mutant is correct, then a very different strategy should be useful when designing inhibitors with enhanced efficacy against this double mutant.
Discussion: The E92Q/N155H mutant's MD exhibited a higher amplitude and frequency of oscillations between open and closed states.
High frequency of integrase Q148R minority variants in HIV-infected patients naive of integrase inhibitors.
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: 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.
HIV mutation literature information.
PMID: 
2011
Antimicrobial agents and chemotherapy
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