Molecular Hybridization-Inspired Optimization of Diarylbenzopyrimidines as HIV-1 Nonnucleoside Reverse Transcriptase Inhibitors with Improved Activity against K103N and E138K Mutants and Pharmacokinetic Profiles.
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, and elvitegravir.
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.
Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis.
Result: Interestingly, these inhibitory effects were not observed with a mutant RT that contained the rilpivirine resistance-associated mutation E138K combined with the two substitutions in the connection subdomain.
Discussion: In addition, recent studies have shown that N348I produces a moderate increase (around 2-fold) in the levels of rilpivirine resistance conferred by E138K, although the reduced DNA polymerase and RNase H activities of the N348I mutant restrict the emergence of the rilpivirine resistance mutation due to the diminished replication capacity of the virus.
Effects of raltegravir or elvitegravir resistance signature mutations on the barrier to dolutegravir resistance in vitro.
PMID: 25691633
2015
Antimicrobial agents and chemotherapy
Abstract: E138K and G140S, as secondary substitutions to Q148H, Q148K, or Q148R, were associated with partial recovery in viral infectivity and/or INSTI resistance.
Abstract: In the Q148H, Q148K, or Q148R mutants, G140S/Q148H, E138K/Q148K, E138K/Q148R, and G140S/Q148R secondary mutations were identified with each INSTI and showed high resistance to RAL o
Global HIV-1 transmitted drug resistance in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.
Method: To obtain a standard interpretation across tests, HIV-1 transmitted drug resistance was defined according to the World Health Organization (WHO) 2009 surveillance list, with the addition of T215N (a revertant of T215F/Y omitted from the list) and E138K (a nonpolymorphic rilpivirine-associated mutation).
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.
Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis.
Result: Nevirapine and efavirenz resistance were predicted in about 1% and 0.5% of virus samples without NNRTI SDRMs as a result of several minimally polymorphic (e.g., A98G, V108I, and V179D) and rare nonpolymorphic (e.g., E138K, G190Q, F227C, and K238T) NNRTI-resistance mutations.
[Resistance profile and genetic barrier of dolutegravir].
PMID: 25858608
2015
Enfermedades infecciosas y microbiologia clinica
Abstract: Dolutegravir displays in vitro activity against mutant HIV-1 harboring any isolated resistance mutations selected during failures to raltegravir or elvitegravir (Y143C/H/, N155H, Q148H/K/R, E92G/Q, T66A/I/K, T97A, E138A/K, G140A/S).
Abstract: The mutations eventually selected (R263K, H51Y and E138K) do not confer significant resistance, and induce a fitness cost that prevents HIV-1 from evading drug pressure.
Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study.
Abstract: Its negative effect was partially compensated by the secondary mutations E138K and G140S.
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: 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 G140S were prepared and cha
Change in the Prevalence of HIV-1 and the Rate of Transmitted Drug-Resistant HIV-1 in Haiphong, Northern Vietnam.
PMID: 25970090
2015
AIDS research and human retroviruses
Abstract: Nonnucleoside RT inhibitor-resistant mutations, Y181C/I, were detected in three subjects; one had the nucleoside RT inhibitor-resistant mutations L74V and M184V and one had E138K.
HIV mutation literature information.
PMID: 
2015
Journal of virology
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