New indolylarylsulfone non-nucleoside reverse transcriptase inhibitors show low nanomolar inhibition of single and double HIV-1 mutant strains.
PMID: 32883642
2020
European journal of medicinal chemistry
Abstract: Among these, IAS 12 exhibited a remarkable antiviral activity against single and double mutants (K103N EC50 = <0.7 nM; Y181C EC50 = <0.7 nM; Y188L EC50 = 21.3 nM; K103N-Y181C EC50 = 6.2 nM), resulting equally or more active than previuosly reported IAS 6 and some approved anti-HIV-1 drugs.
Abstract: Docking and molecular dynamics simulations of compound 12 in complex with WT, Y181C, Y188L, K103N and K103N-Y181C RTs clarified a general binding mode that was consistent with biological results.
Abstract: Kinetic experiments disclosed that derivative 12 preferentially binds WT and
Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development.
PMID: 32925358
2020
Journal of acquired immune deficiency syndromes (1999)
Abstract: DOR was rationally designed to address limitations associated with other approved NNRTIs, particularly resistance from common NNRTI resistance-associated mutants containing K103N, Y181C, or G190A reverse transcriptase substitutions.
Introduction: By contrast, under the same conditions, RT substitutions L100I and K103N were the major substitutions associated with EFV, and E138K and K101P substitutions were the 2 most common resistance pathways in selection studies with RPV.
Introduction: DOR was rationally designed to address limitations associated with other approved PMID: 32946725
2020
Emerging infectious diseases
Abstract: Phylogenetic and network analysis elucidated numerous cases of shared drug resistance mutations among genetically linked patients; K103N was the most frequently shared mutation.
Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania.
Abstract: Frequent NNRTI-resistance associated mutations were K103N (n = 11), V106M (n = 5) and G190A (n = 5).
Result: The most frequent NNRTI resistance-associated mutations were K103N (44%), V106M (20%), and G190A (20%) (Fig 3), all of these three mutations confer high-level resistance to efavirenz and nevirapine.
Table: K103N
Discussion: The most frequent NNRTI resistance-associated mutations were K103N, V106M, and G190A that confer high-level resistance to efavirenz and nevirapine.
Increased HIV-1 pretreatment drug resistance with consistent clade homogeneity among ART-naive HIV-1 infected individuals in Ethiopia.
Abstract: The most frequently observed NNRTIs-associated mutations common to both algorithms were K103N (2%), Y188L (2%), K101E (2%), and V106A (2%), while E138A (2%) was observed according to IAS-USA only.
Result: Both CPR tool and IAS-USA algorithms were concordant in identifying five NNRTIs resistance-associated mutations: K103N in one p
Table: K103N
Discussion: In agreement with our report, K101E, K103N, and E138A mutations of the RT region had been reported previously in Ethiopia among ART-naive individuals.
Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen.
Abstract: Over the past 40 years, the frequency of the DRM M184V (50-64.3%, p=0.363), G190A (17.2-46.2%, p=0.021), and K103N (34.5-42.3%, p=0.551) increased, while the frequency of Y181C (17.2-7.7%, p=0.289) decreased.
Abstract: The major DRM in the NRTIs was the M184V, whereas the G190A, K103N, and Y181C were the major DRMs in the NNRTIs.
Transmitted and Acquired HIV-1 Drug Resistance from a Family: A Case Study.
Abstract: Mother also acquired K101E (41.03%), K103N (27.56%) and minor mutation of V106M (4.30%) after improperly discontinuing antiretroviral regimen of lamivudine (3TC), tenofovir (TDF) and efavirenz (EFV).
Introduction: A major disadvantage of EFV is the low genetic barrier that certain single amino acid mutation, such as K103N, V106M, can cause a high level of drug resistance.
Result: However, for patient M, V106M alone is associated with a high-level reduction in NVP (60) and EFV (60) susceptibility as well as an intermediate reduction in DOR (50) susceptibility, while together with V106I, especially K101E and K103N, the mutation scores are increased to 65, 135,
High Prevalence of HIV-1 Drug Resistance and Dynamics of Transmission Among High-Risk Populations in Port-au-Prince, Haiti.
PMID: 33136738
2020
Journal of acquired immune deficiency syndromes (1999)
Abstract: Five clusters (62.5%) had shared DRMs, and K103N and M184V were the main shared mutations.
Result: Five clusters had shared resistance mutations, and K103N (14/24) and M184V (12/24) were the main DRM shared.
Result: Of the DRM, K103N (46/119; 38.6%), which causes high-level resistance to efavirenz and nevirapine, and M184V (35/119; 29.4%), associated with TDF and Emtricitabine (FTC) resistance, were the most frequently observed.
Result: Resistance mutations were detected in 1 of the 5 individuals classified as recently infected (NNRTI: K103N; K101E).
In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix.
Result: Baseline genotype (pre-PI) indicated that the individual had developed extensive resistance to first-line ART, with the nucleoside reverse transcriptase inhibitor (NRTI) mutations K65R and M184I conferring high-level tenofovir and lamivudine resistance, respectively, as well as K103N and Y181C conferring resistance to nonnucleoside reverse transcriptase inhibitors (NNRTI).
Result: Of note, we observed loss of mutations affecting susceptibility to lamivudine (M184I), tenofovir (K65R), and efavirenz (K103N) between baseline and VF1.
HIV mutation literature information.
PMID: 
2020
European journal of medicinal chemistry
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