HIV-1 Integrase Inhibitors That Are Active against Drug-Resistant Integrase Mutants.
PMID: 32601157
2020
Antimicrobial agents and chemotherapy
Abstract: Both were superior to DTG, as evidenced by the data obtained with the IN mutant T66I/L74M/E138K/S147G/Q148R/S230N, which was selected by CAB using an EVG-resistant lab strain.
Bioisosterism-based design and enantiomeric profiling of chiral hydroxyl-substituted biphenyl-diarylpyrimidine nonnucleoside HIV-1 reverse transcriptase inhibitors.
PMID: 32712537
2020
European journal of medicinal chemistry
Abstract: Among all the chiral derivatives, (S)-(-)-12a showed the best potency with the antiviral activities against wild-type (WT) and single mutant strains (L100I, K103 N, Y181C, E138K; especially Y188L), and RT enzyme in the low nanomolar concentration range.
Prevalence and determinants of resistance mutations in HIV-1-infected patients exposed to integrase inhibitors in a large Italian cohort.
Abstract: Overall, the Q148H/K/R plus G140A/C/S and/or E138A/K/T pattern, defining an intermediate level of resistance to DTG, was detected in 70 (15%) cases.
Abstract: The most frequent INSTI resistance mutation was N155H, followed by Q148H/K/R, G140A/C/S, E138A/K/T and Y143C/H/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: 30721060
2019
Journal of medicinal chemistry
Abstract: Diarylpyrimidine derivatives (DAPYs) exhibit robust anti-HIV-1 potency, although they have been compromised by E138K variant and severe side-effects and been suffering from poor water solubility.
Abstract: The anti-HIV-1 activities of 11c (EC50(WT) = 0.0035 muM, EC50(E138K) = 0.0075 muM) were the same as and 2-fold better than that of the lead etravirine against the wild-type and E138K mutant HIV-1, respectively, with a relative low cytotoxicity (CC50 >= 173 muM).
Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort.
Introduction: However, the landscape of antiretrovirals is changing continuously and new mutations such as E138A/G/K/Q/R (that confers resistance to the NNRTI rilpivirine (RPV), approved in 2011) are therefore not covered by this list.
Result: Mutations E138A/G/K/R were found in 99 of 186 viruses (52.9%) showing RPV resistance, which account for 40% of all NNRTI-resistant viruses.
Result: The most common TDRMs found in baseline samples were the T215 revertants, followed by E138A/G/K/Q/R, K103NS, V179DE and M41L (S1 Table).
Discussion: Competition experiments have shown that E138A
Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance.
PMID: 30648124
2019
Open forum infectious diseases
Introduction: A number of additional mutations observed in patients can increase DTG resistance, including L74M and E138K.
High Levels of HIV-1 Drug Resistance in Children Who Acquired HIV Infection Through Mother to Child Transmission in the Era of Option B+, Haiti, 2013 to 2014.
PMID: 30640198
2019
The Pediatric infectious disease journal
Result: Twenty-nine (9.5%) of the children had additional NNRTI mutations (A98G, E138A/G/K/Q, H221Y, and M230L) that confer resistance to second generation NNRTI drugs etravirine and rilpivirine.
Identification of Dihydrofuro[3,4- d]pyrimidine Derivatives as Novel HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors with Promising Antiviral Activities and Desirable Physicochemical Properties.
PMID: 30624934
2019
Journal of medicinal chemistry
Conclusion: Especially, 13c2 and 13c4 proved to be the exceptionally potent inhibitors, exhibiting EC50 values of 0.9-7.0 nM against single NNRTI-resistant strains L100I, K103N, Y181C, Y188L, and E138K in MT-4 cells and bringing approximately 1.3- to 3.6 fold improvement in potency compared with ETV (EC50 = 3.3-20.4 nM).
Result: As noted above, 13c2 can inhibit single (L100I, K103N, Y181C, Y188L, E138K) and double (F227+V106A) mutated HIV-RT variants (see Figure S3 for the location of these mutations).
Result: In the case of
Discovery of potent HIV-1 non-nucleoside reverse transcriptase inhibitors by exploring the structure-activity relationship of solvent-exposed regions I.
PMID: 30381875
2019
Chemical biology & drug design
Abstract: Especially, against the mutant strains K103N and E138K, most compounds exhibited more potent activity than against WT HIV-1.
Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted Human Immunodeficiency Virus Type 1 Drug Resistance in a Large US Clinic Population.
Method: Several additional DRMs not on the SDRM list were analyzed including (1) the primarily tenofovir disoproxil fumarate (TDF)-selected DRMs A62V, K65N, and K70G/N/Q/S/T and (2) the primarily rilpivirine (RPV)-selected DRMs E138A/G/K/Q, of which E138A is polymorphic, occurring in 1%-4% of viruses from ART-naive individuals.
Result: The mutations E138A/G/K/Q, which are associated with reduced RPV susceptibility but are not on the SDRM list, occurred in 99 individuals, including 90 without an SDRM.
HIV mutation literature information.
PMID: 
2020
Antimicrobial agents and chemotherapy
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