Abstract: One NRTI-associated (M184V/I) and three NNRTI-associated (K103N/S, Y181C/I and G190A/S) mutations had high percentages in ART-naive and ART-treated individuals, and these mutations conferred high-level resistance to 3TC, EFV and/or NVP.
Introduction: In addition, we report high percentages of one NRTI (M184V/I) and three NNRTI (K103N/S, Y181C/I and G190A/S) mutations in ART-naive and ART-treated individuals, which confer high-level resistance to 3TC, EFV and/or NVP.
Discussion:
Prevalence of HIV-1 Drug-Resistance Genotypes Among Unique Recombinant Forms from Yunnan Province, China in 2016-2017.
PMID: 31914782
2020
AIDS research and human retroviruses
Abstract: Mutations such as M184V/I (35.4%) in NRTIs and K103N/R/S/T (25.4%), V179D/E/T/Y (18.9%), G190A/E/R/S (13.8%), and Y181C (9.2%) in NNRTIs were common among the HIV-1 URF strains relative to other mutations.
Pretreatment HIV drug resistance spread within transmission clusters in Mexico City.
PMID: 31819984
2020
The Journal of antimicrobial chemotherapy
Abstract: Among all persons sharing DRMs, those sharing K103N were younger (aOR = 0.93, 95% CI 0.88-0.98, P = 0.003).
Abstract: Among clustering individuals, 175/963 (18%) shared DRMs (involving 66 clusters), of which 66/175 (38%) shared K103N/S (24 clusters).
Discussion: Moreover, the higher odds of sharing K103N between younger persons and in smaller clusters also suggests important groups for intervention.
Discussion: Propagation of K103N within the network is noteworthy, and of high relevance not only to Mexico but also to many other resource-limited countries that still use efavirenz-based first-line ART regimens without availability of baseline HIV genotyping and weak viral load monitoring systems.
Discussion: Sharing of specific DRMs was common, especially K103N/S, revealin
Evaluation of the management of pretreatment HIV drug resistance by oligonucleotide ligation assay: a randomised controlled trial.
Abstract: The OLA-guided therapy group had pre-ART peripheral blood mononuclear cells evaluated for drug resistance to non-nucleoside reverse transcriptase inhibitor (NNRTI) at codons Lys103Asn, Tyr181Cys, Gly190Ala, and to lamivudine at Met184Val, and when at least one drug-resistant codon was detected in a participant's pre-ART specimen, clinicians were directed to prescribe protease inhibitor-based second-line ART.
Method: Peripheral blood mononuclear cells were evaluated for NNRTI and NRTI drug resistance mutations, K103N, Y181C, G190A, and
Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I.
PMID: 31774913
2020
The Journal of infectious diseases
Result: The viral isolate tested also had NNRTI resistance mutations A98G, K103N, and P225H.
Indazolyl-substituted piperidin-4-yl-aminopyrimidines as HIV-1 NNRTIs: Design, synthesis and biological activities.
PMID: 31767136
2020
European journal of medicinal chemistry
Abstract: And also, it displayed potent activities against K103 N (EC50 = 0.077 muM), Y181C (EC50 = 0.11 muM), E138K (EC50 = 0.057 muM), and moderate activity against double mutants RES056 (EC50 = 8.7 muM).
Fragment hopping-based discovery of novel sulfinylacetamide-diarylpyrimidines (DAPYs) as HIV-1 nonnucleoside reverse transcriptase inhibitors.
PMID: 31735575
2020
European journal of medicinal chemistry
Abstract: Further optimization on the sulfur led to the sulfinylacetamide-DAPYs exhibiting improved anti-viral activity and a higher selectivity index especially toward the K103N mutant strain.
Abstract: The most potent compound 12a displayed EC50 values of 0.0249 muM against WT and 0.0104 muM against the K103N mutant strain, low cytotoxicity (CC50 > 221 muM) and a high selectivity index (SI WT > 8873, SI K103N > 21186).
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: Substituent modifications resulted in the identification of new DABPs with the combination of the strengths of the two drugs, especially compound 12d, which showed promising activity toward the EFV-resistant K103N mutant.
Abstract: The antiviral activity of this compound was much higher than those of ETR and EFV against the WT, E138K, and K103N variants (EC50 = 3.4, 4.3, and 3.6 nM, respectively), and the cytotoxicity was decreased while the selectivity index (SI) was increased.
Effect of alpha-Methoxy Substitution on the Anti-HIV Activity of Dihydropyrimidin-4(3 H)-ones.
PMID: 30525601
2019
Journal of medicinal chemistry
1Abstract: The various alpha-methoxy DABO series (12-14) present different SAR at the dihalo benzyl substitution, with the most potent compounds (12d,e and 13c) showing similar (picomolar/nanomolar) anti-HIV-1 potency as the corresponding alpha-methyl analogues against wt HIV-1, and 10-100-fold increased potency (up to low nanomolar) against clinically relevant K103N, Y181C, Y188L, IRLL98, and K103N+Y181C HIV-1 mutant strains, highlighting the importance of the alpha-methoxy substitution to provide highly efficient DABOs as ""second generation"" NNRTIs."
Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted Human Immunodeficiency Virus Type 1 Drug Resistance in a Large US Clinic Population.
Result: The mutations K103N/S, Y181C, Y188L, and G190A accounted for 88.5% of the 348 NNRTI SDRMs.
Figure: One individual (PID 50) was also primarily infected with this virus as a 2002 sequence obtained prior to therapy contained Y181C + L90M (indicated in red with an open triangle) and later developed K103N (indicated in black with a closed triangle) after receiving multiple nucleoside reverse transcriptase inhibitor regimens followed by tenofovir/emtricitabine/efavirenz in combination with atazanavir/ritonavir and then raltegravir.
HIV mutation literature information.
PMID: 
2020
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