Development of a G118R mutation in HIV-1 integrase following a switch to dolutegravir monotherapy leading to cross-resistance to integrase inhibitors.
PMID: 27029845
2016
The Journal of antimicrobial chemotherapy
Abstract: CONCLUSIONS: Although resistance to dolutegravir is typically rare, genetic polymorphisms and monotherapy can facilitate the acquisition of G118R.
Abstract: Cell culture selections and phenotypic drug susceptibility assays assessed resistance via the G118R pathway.
Abstract: Cell culture selections were used to assess the in vitro progression of the G118R pathway leading to cross-resistance to all integrase inhibitors.
Abstract: In this study, rapid development of the G118R mutation arose following a switch from first-line elvitegravir/cobicistat/tenofovir disoproxil fumarate/emtricitabine to dolutegravir monotherapy.
Abstract: The appearance of G118R in these two cases and subtype C and CRF02_AG in vitro selections were related to a rare GGA natu
Development of a G118R mutation in HIV-1 integrase following a switch to dolutegravir monotherapy leading to cross-resistance to integrase inhibitors.
PMID: 25414202
2015
The Journal of antimicrobial chemotherapy
Abstract: Interestingly, the F121Y mutation, but not the G118R mutation, displayed differential resistance to raltegravir and dolutegravir.
Abstract: METHODS: Both the F121Y and G118R mutations were introduced by site-directed mutagenesis into the pNL4.3 backbone and studied in cell-based and in vitro assays.
Abstract: The aim of this study was to characterize the susceptibility of two mutations, F121Y and G118R, originally described in patients failing raltegravir-containing regimens, to dolutegravir and raltegravir, and then to compare the resistance of these mutations with that of other well-known mutations involved in raltegravir resistance.
Development of a G118R mutation in HIV-1 integrase following a switch to dolutegravir monotherapy leading to cross-resistance to integrase inhibitors.
Abstract: By characterizing the G118R substitution, this work also preemptively defines parameters for a potentially important pathway in some non-B HIV subtype viruses treated with dolutegravir and will aid in the inhibition of such a virus, if detected.
Abstract: In cell-free experiments, the impacts of the H51Y and E138K substitutions on resistance and enzyme efficiency, when present with G118R, were highly dependent on viral subtype.
Abstract: Subtype B and circulating recombinant form AG (CRF02_AG) clonal viruses encoding G118R-bearing integrases were severely restricted in their viral replication capacity, and G118R/E138K-bearing viruses had various levels of resistance to dolutegravir, raltegravir,
Simian-tropic HIV as a model to study drug resistance against integrase inhibitors.
PMID: 25583721
2015
Antimicrobial agents and chemotherapy
Abstract: Here, we used a T-cell-tropic SIV/HIV recombinant virus in which the capsid and vif regions of HIV-1 were replaced with their SIV counterparts (simian-tropic HIV-1 [stHIV-1](SCA,SVIF)) to study the impact of a number of drug resistance substitutions in the integrase coding region at positions E92Q, G118R, E138K, Y143R, S153Y, N155H, and R263K on drug resistance, viral infectivity, and viral replication capacity.
In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2.
Result: In addition, the roles of novel INSTI-associated changes (i.e, H51Y, G118R, F121Y, E138A/K, and R263K) remain to be determined in HIV-2, and the level of dolutegravir resistance in vitro that correlates with virologic failure in HIV-2-infected patients is unknown.
Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study.
Abstract: Primary substitution G118R had different influence on the activity of proteins of the subtypes A and B, and the compensatory effect of the secondary substitution E138K also depended on the viral subtype.
Abstract: The substitution G118R slightly reduced the efficiency of IN inhibition by raltegravir and elvitegravir and caused no resistance to XZ_259.
Abstract: To assess the impact of drug resistance mutations on the activity of IN of HIV-1 subtype A strain FSU-A, which is dominant in Russia, variants of the consensus IN of this subtype containing the primary resistance mutations G118R and Q148K and secondary compensatory substitutions E138K and PMID: 26372484
2015
AIDS (London, England)
Abstract: DESIGN AND METHODS: We performed tissue culture selection experiments using DTG-resistant viruses containing integrase substitutions at positions R263K, H51Y/R263K, E138K/R263K, G118R and H51Y/G118R in the presence of increasing concentrations of either RAL or EVG.
Abstract: The most common substitution in integrase under those circumstances is R263K whereas another substitution that was selected against DTG in tissue culture was G118R.
Characterization of the Drug Resistance Profiles of Integrase Strand Transfer Inhibitors in Simian Immunodeficiency Virus SIVmac239.
Abstract: The results show that the G118R and G140S Q148R substitutions decreased Km' and Vmax'/Km' for strand transfer compared to those of the WT.
Abstract: To study this at a biochemical level, purified recombinant SIVmac239 wild-type (WT) and E92Q, T97A, G118R, Y143R, Q148R, N155H, R263K, E92Q T97A, E92Q Y143R, R263K H51Y, and G140S Q148R
Effect of HIV-1 integrase resistance mutations when introduced into SIVmac239 on susceptibility to integrase strand transfer inhibitors.
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.
New raltegravir resistance pathways induce broad cross-resistance to all currently used integrase inhibitors.
PMID: 24710029
2014
The Journal of antimicrobial chemotherapy
Abstract: CONCLUSIONS: This study showed that G118R and F121Y mutations, rarely described in patients failing on raltegravir, induced broad cross-resistance to all currently used integrase inhibitors.
Abstract: In silico, results showed that G118R and F121Y enzymes were associated with reduced binding affinities to each of the inhibitors and with a decreased number of hydrogen bonds compared with the wild-type complexes.
Abstract: METHODS: The behaviour of integrases with mutations G118R and F121Y towards raltegravir, elvitegravir and dolutegravir was analysed by evaluating phenotypic susceptibility and by means of in silico techniques (investigating binding affinities and the stabilization of the inhibi
HIV mutation literature information.
PMID: 
2016
The Journal of antimicrobial chemotherapy
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