Abstract: E138K is likely to cause cross-resistance to other NNRTIs thereby limiting the further utilization of this class.
Abstract: The most common mutation that emerged during RPV therapy was E138K, which often occurred in combination with M184I.
Biochemical mechanism of HIV-1 resistance to rilpivirine.
PMID: 22955279
2012
The Journal of biological chemistry
Abstract: Quantum mechanics/molecular mechanics hybrid molecular modeling revealed that p51(E138K) affects access to the RPV binding site by disrupting the salt bridge between p51(E138) and p66(K101).
Abstract: Virological failure during therapy with RPV and emtricitabine is associated with the appearance of E138K and M184I mutations in RT.
Abstract: We compared WT with four subunit-specific RT mutants, p66(M184I)/p51(WT), p66(E138K)/p51(E138K), p66(E138K/M184I)/p51(E138K), and p66(M184I)/p51(E138K).
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: Accordingly, we performed tissue culture studies to investigate the evolutionary dynamics of E138K in both a wild-type (WT) and a Y181C background.
Abstract: However, E138K can be consistently selected by ETR when wild-type viruses but not viruses containing Y181C are grown in tissue culture.
Abstract: The addition of E138K to Y181C also decreased the level of resistance to ETR compared to that obtained with Y181C alone.
Abstract: This study was carried out to evaluate any possible mechanisms that might explain antagonism between the Y181C and E138K mutations.
Abstract: We also generated recombinant enzymes containing
"Prolonged and substantial discordance in prevalence of raltegravir-resistant HIV-1 in plasma versus PBMC samples revealed by 454 ""deep"" sequencing."
Introduction: E138K and G140S are secondary mutations that develop following the detection of Q148K/R, restoring viral infectivity and replication kinetics.
Method: Secondary raltegravir-associated DRMs were defined to be E92V, Q95K, T97A, F121Y, E138A/K, G140A/C/S, S147G, V151A/I/L, M154I/L, E157Q, and G163K/R, and linkages examined were T97A and Y143C/R,
Molecular Hybridization-Inspired Optimization of Diarylbenzopyrimidines as HIV-1 Nonnucleoside Reverse Transcriptase Inhibitors with Improved Activity against K103N and E138K Mutants and Pharmacokinetic Profiles.
PMID: 21135184
2011
Antimicrobial agents and chemotherapy
Abstract: The results show that ETR selected mutations at positions V90I, K101Q, E138K, V179D/E/F, Y181C, V189I, G190E, H221H/Y, and M230L and that E138K was the first of these to emerge in most instances.
Abstract: Viral clones containing E138K displayed low-level phenotypic resistance to ETR (3.8-fold) and modestly impaired replication capacity (2-fold) compared to wild-type virus.
Abstract: We identified K101Q, E138K, V179E, V189I,
Synthesis and biological evaluation of 6-substituted 5-alkyl-2-(phenylaminocarbonylmethylthio)pyrimidin-4(3H)-ones as potent HIV-1 NNRTIs.
Abstract: Among them, 2-[(4-cyanophenylamino)carbonylmethylthio]-6-(2-chloro-6-fluorobenzyl)-5-ethylpyrimidin-4(3H)-one 4 b6 is one of the compounds endowed with the highest broad-spectrum HIV-1 inhibitory activity, with EC(50) values of 0.19+-0.005 muM against the wild-type virus, 1.05+-0.24 muM (twofold resistance) against the E138K strain, and 2.38+-0.13 muM (4.5-fold resistance) against the Y181C strain.
Effect of mutations at position E138 in HIV-1 reverse transcriptase on phenotypic susceptibility and virologic response to etravirine.
PMID: 21637112
2011
Journal of acquired immune deficiency syndromes (1999)
Abstract: Site-directed mutants harboring E138A/G/K/Q/R or S showed etravirine fold change values of 2.9, 2.4, 2.6, 3.0, 3.6, and 2.8, respectively.
Switching between raltegravir resistance pathways analyzed by deep sequencing.
Result: The Q148K + E138K combination was evident at month 3, and though this combination is reported to be a potent RAL escape variant, it was not detected subsequently.
Interaction of reverse transcriptase (RT) mutations conferring resistance to lamivudine and etravirine: effects on fitness and RT activity of human immunodeficiency virus type 1.
Abstract: Clinical trials of RPV administered with lamivudine or emtricitabine showed the emergence of E138K together with M184I, which confers lamivudine and emtricitabine resistance in most patients with virologic failure.
Abstract: Fitness profiles and growth competition experiments showed that the E138K/M184I mutant had a significant replicative advantage over the E138K/M184V mutant in the presence of etravirine and lamivudine.
Abstract: Resistance to the nonnucleoside reverse transcriptase inhibitors etravirine and rilpivirine (RPV) is conferred by the E138K mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (Nonnucleoside Reverse Transcriptase Inhibitors with Improved Activity against K103N and E138K Mutants and Pharmacokinetic Profiles.
Abstract: RT enzymes containing E138K, E138K/184I, or E138K/184V exhibited higher processivity than WT RT at low dNTP concentrations.
Abstract: E138K restored viral replication capacity (RC) in the presence of M184I/V, and this was confirmed in cell-free RT processivity assays.
Abstract: Recently, several phase 3 clinical trials (ECHO and THRIVE) showed that E138K and M184I were the most frequent mutations to emerge in patients who failed therapy with rilpivirine (RPV) together with two nucleos(t)ide reverse transcriptase inhibitors, emtricitabine (FTC) and tenofovir (TDF).
HIV mutation literature information.
PMID: 
2012
Antiviral therapy
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