Discussion: Cooperative effects were also observed between the E92Q and Y143C replacements in HIV-2 integrase; although these changes individually had no measurable effect on raltegravir sensitivity, the E92Q with Y143C enzyme was approximately 10-fold resistant to the inhibitor.
Discussion: Studies of HIV-1 patients have identified three principal mutational patterns that emerge in response to raltegravir treatment: Q148H/K/R with or without G140S/A, N155H with or without E92Q and Y143C/R with or without T97A.
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.
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.
Introduction: In vitro, several mutations have been introduced into the IN gene and activities of mutants have been determined (T66I, L74M, E92Q, F121Y, Q148K, S153Y, N155H).
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
Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness.
PMID: 20634701
2010
Journal of acquired immune deficiency syndromes (1999)
Result: By contrast, the E92Q/N155H mutant was fitter than the E138K/Q148H mutant both in the absence and presence of 5.0 microM RAL (Table 2).
Result: In these experiments, the Q148H/G140S recombinant was substantially fitter than E92Q/N155H both in the absence and presence of raltegravir (Fig.2).
Result: Introduction of E92Q or G163R into an N155H backbone resulted in a virus with greater fitness than N155H mutant both in the absence and presence of RAL.
Result: The addition of secondary mutations L74M or
HIV-1 subtype B and C integrase enzymes exhibit differential patterns of resistance to integrase inhibitors in biochemical assays.
Abstract: CONCLUSION: Polymorphic differences within the subtype B and C integrase genes likely cause variations in the contribution of N155H alone or in combination with E92Q to drug resistance.
Abstract: METHODS: We compared the susceptibility of subtype B and C HIV-1 integrase enzymes, harboring the previously reported resistance mutations E92Q, N155H, and E92Q/N155H, to clinically relevant integrase inhibitors.
Abstract: RESULTS: Subtype C integrase enzymes bearing the resistance mutations E92Q/N155H were approximately 10-fold more susceptible to each of two
Discovery of potent HIV integrase inhibitors active against raltegravir resistant viruses.
Abstract: Several compounds with excellent activities against wild-type virus as well as against the viruses with the mutations Q148H/G140S or N155H/E92Q were reported.
Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors.
Introduction: In the patients enrolled for elvitegravir (EVG) studies, T66I, E92Q, Q148R and N155H mutations are primary contributors to EVG resistance.
Update of the drug resistance mutations in HIV-1: December 2010.
Abstract: This update includes 9 new mutations- E138G and E138K for etravirine (Haddad M et al, CROI, 2010; Abstract 574, and Vingerhoets J et al, Antivir Ther, 2010;15 [Suppl 2]:A125); E92Q for raltegravir (Geretti AM et al, Antivir Ther, 2010;15 [Suppl 2]:A62; Cooper et al, N Engl J Med, 2008;359:355-365; and Malet I et al, Antimicrob Agents Chemother, 2008;52:1351-1358); and M36L, M36V, H69R, L89I, L89M, and L89V for tipranavir/ritonavir.
Extended use of raltegravir in the treatment of HIV-1 infection: optimizing therapy.
HIV mutation literature information.
PMID: 
2011
AIDS (London, England)
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