Abstract: DTG remained fully effective against all site-directed mutants except G118R and R263K.
Abstract: Each of the G118R, Y143R, Q148R, R263K, and G140S/Q148R mutations, when introduced into SIV, impaired infectiousness and replication fitness compared to wild-type virus.
Abstract: Using TZM-bl cells, we demonstrated that the Q148R and N155H mutational pathways conferred resistance to EVG (36- and 62-fold, respectively), whereas R263K also displayed moderate resistance to EVG (12-fold).
HIV Drug Resistance and the Advent of Integrase Inhibitors.
PMID: 23180144
2013
Current infectious disease reports
Abstract: Here, we provide new information about the most recent mutations identified and other mutations that confer resistance to several integrase inhibitors, such as new resistance mutations-for example, G118R, R263K, and S153Y-that have been identified through in vitro selection studies with second-generation integrase strand transfer inhibitors (INSTIs).
Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure.
Conclusion: R263K, could potentially be advantageous not only for HIV treatment but for strategies aimed at HIV eradication as well.
Table: R263K
Figure: (A) Recombinant integrase proteins INWT, INH51Y, INR263K, and INH51Y/R263K were purified (lanes 2 to 5) and (B) used to measure
Figure: (A) pNL4.3IN(WT), pNL4.3IN(H51Y), pNL4.3IN(R263K), and pNL4.3IN(H51Y/R263K) infectivity were measured by quantifying luciferase activity in relative luminescent units (RLU) produced by TZM-bl cells infected with increasing concentrations of virus (in ng of p24 antigen).
Biochemical analysis of the role of G118R-linked dolutegravir drug resistance substitutions in HIV-1 integrase.
PMID: 24080645
2013
Antimicrobial agents and chemotherapy
Abstract: The G118R substitution therefore represents a potential avenue for resistance to DTG, similar to that previously described for the R263K substitution.
Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics.
Introduction: In addition, in the ART-experienced, INSTI-naive SAILING study, 16 patients in the RAL group had typical treatment-emergent RAL resistance with high fold-changes to RAL, and 2 patients receiving DTG developed the IN substitution R263K, which conferred fold-changes of <2.
HIV-1 integrase resistance among antiretroviral treatment naive and experienced patients from Northwestern Poland.
Abstract: Other variants included L68V, L74IL, T97A, E138D, V151I, R263K.
Result: Among virologically failing patients E157Q was noted in one patient with N155H mutant, in three E157Q variant was present at baseline and consistently in the sequences obtained on RAL therapy while in two patients either R263K or L74IL were present at baseline and disappeared in the subsequent sequences on virologically unsuccessful treatment.
Result: Other mutations and polymorphisms observed only in subtype B integrase sequences were L68V,
The development of novel HIV integrase inhibitors and the problem of drug resistance.
Abstract: Several newly identified resistance mutations, such as G118R, R263K and S153Y, have been identified through tissue culture selection studies with second-generation integrase strand-transfer inhibitors (INSTIs).
Resistance to HIV integrase inhibitors.
PMID: 22789986
2012
Current opinion in HIV and AIDS
Abstract: RECENT FINDINGS: New resistance mutations, such as G118R, R263K and S153Y, have been recently identified through in-vitro selection studies with second-generation integrase strand-transfer inhibitors (INSTIs).
Progressive emergence of an S153F plus R263K combination of integrase mutations in the proviral DNA of one individual successfully treated with dolutegravir.
Abstract: Biochemical cell-free assays performed with purified IN enzyme containing R263K confirmed the absence of major resistance against DTG and showed a slight decrease in 3' processing and strand transfer activities compared to the wild type.
Abstract: Further analysis by site-directed mutagenesis showed that R263K does confer low-level resistance to DTG and decreased integration in cell culture without altering reverse transcription.
Abstract: Structural modeling suggested and in vitro IN-DNA binding assays show that the R263K mutation affects IN-DNA interactions.
Abstract: Therefore, we performed in vitro selection experiments with DTG using viruses of subtypes B, C, and A/G and showed that the most common mutation to emerg
In vitro resistance selections using elvitegravir, raltegravir, and two metabolites of elvitegravir M1 and M4.
Abstract: Additional resistance selection experiments using elvitegravir led to the development of previously reported integrase inhibitor resistance mutations (T66I, F121Y, and S153Y) as well as a novel R263K integrase mutation.
HIV mutation literature information.
PMID: 
2014
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