HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters.
PMID: 28472323
2017
The Journal of antimicrobial chemotherapy
Discussion: The emergence of select mutations under dolutegravir pressure, including R263K (AGA AAA or AGG AAG), G163R (GGA AGA or GGG AGG) and E138K (GAA AAA, GAG AAG), may be related to APOBEC-mediated G A hypermutation.
Drug-like property-driven optimization of 4-substituted 1,5-diarylanilines as potent HIV-1 non-nucleoside reverse transcriptase inhibitors against rilpivirine-resistant mutant virus.
Abstract: Newly synthesized p-cyanovinyl-DAANs (8a-8g) with different R1 side chains plus prior active p-cyanoethyl-DAANs (4a-4c) were evaluated not only for anti-HIV potency against both wild-type HIV virus and rilpivirine-resistant (E138K, E138K+M184I) viral replication, but also for multiple drug-like properties, including aqueous solubility, lipophilicity, and metabolic stability in human liver microsomes and human plasma.
Abstract: This study revealed that both ester and amide R1 substituents led to low nanomolar anti-HIV potency against wild-type and rilpivirine-resistant viral strains (E138K-resistance fold changes<3).
Introduction: Furthermore, these same DAANs also inhibited the E138K+M184I viral strain with resistance FCs ranging from 1.4 to 6.3, better than or sim
Etravirine combined with antiretrovirals other than darunavir/ritonavir for HIV-1-infected, treatment-experienced adults: Week 48 results of a phase IV trial.
Method: Primary INSTI RAMs against EVG and/or RAL were based on IAS-USA Guidelines of RAMs with some modifications to remove secondary INSTI RAMs (i.e., L74M, F121Y, E138A/K, and G140A/S) (Fig 1).
HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China.
Performance of Celera RUO integrase resistance assay across multiple HIV-1 subtypes.
PMID: 27993614
2017
Journal of virological methods
Abstract: Mutations associated with integrase resistance were observed in seven of the 106 (7%) clinical samples [one sample: Q148K; E138K; G140A; two samples: T97A and four samples: L74I].
Result: The following mutations were observed: Q148K; E138K; G140A in one sample; T97A in two samples; and L74I in four samples.
Recent trends and patterns in HIV-1 transmitted drug resistance in the United Kingdom.
Method: In this report, the term 'transmitted drug resistance mutations' (TDRMs) is used to describe (a) for pol, the presence of one or more mutations from the World Health Organisation (WHO) 2009 surveillance list 19 with the addition of E138K, a mutation known to cause resistance to the second-generation nonnucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine, and all changes at codon T215 as they are likely to be ancestrally related to T215F or Y mutations 20; (b) for integrase, the presence of mutations from the IAS-USA 2013 list or accessory mutations reported by the Stanford HIVdb algorithm v7.0 (HIV Drug Resistance Database, Stanford University, Stanford, CA).
Prevalence of integrase inhibitor resistance mutations in Austrian patients recently diagnosed with HIV from 2008 to 2013.
Abstract: Two patients carried the accessory mutations E138K and G140A, respectively, where both lie on the Q148 pathway.
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: 27070547
2016
Journal of medicinal chemistry
Abstract: Compounds 6a, 14c, and 14d showed high potency against the 1b-resistant E138K mutated viral strain as well as good balance between anti-HIV-1 activity and desirable druglike properties.
Abstract: From the perspective of optimizing future NNRTI compounds as clinical trial candidates, computational modeling results provided valuable information about how the R(1) group might provide greater efficacy against the E138K mutant.
Abstract: Three series (6, 13, and 14) of new diarylaniline (DAAN) analogues were designed, synthesized, and evaluated for anti-HIV potency, especially against the E138K viral strain with a major mutation conferring resistance to the new-generation non-nucleoside reverse transcriptase inhibitor drug rilpivirine (1b).
HIV mutation literature information.
PMID: 
2017
The Journal of antimicrobial chemotherapy
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