Result: In this study,19 substitutions conferring major resistance to DTG at 10 amino acid positions in the IN (T66A/I/K, E92G, G118R, E138K/A/T, G140S/A/C, Result: No major DRMs known to be associated with DTG resistance (T66K, E92Q, G118R, E138K/A/T, G140S/A/C, Q148H/R/K, N155H, or R263K) were detected among INSTI- naive individuals, regardless of previous exposure to ART.
Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine.
PMID: 34978890
2022
Antimicrobial agents and chemotherapy
Introduction: Although L74I has not been observed in association with INSTI resistance (https://hivdb.stanford.edu/dr-summary/resistance-notes/INSTI/), the L74M mutation in combination with INSTI resistance-associated mutations (RAMs) T66I/K, E92V, Y143C, or N155H reduced susceptibility 14- to >200-fold to raltegravir or elvitegravir.
Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study.
Method: INSTI mutations, which are not included on this list, were defined as those on the Stanford HIVdb surveillance DRM list, namely T66AIK, E92Q, F121Y, G140ACS, Y143CHR, S147G, Q148HKR and N155HS.
HIV-1 Subtype C Drug Resistance Mutations in Heavily Treated Patients Failing Integrase Strand Transfer Inhibitor-Based Regimens in Botswana.
Method: The mutations of interest included: T66A/I/K, E92Q, G118R, E138K/A/T, G140S/A/C, Y143R/C/H, S147G, Q148H/R/K, N155H and R263K.
Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV.
Method: Patients with the following baseline mutations associated with reduced susceptibility to DTG: T66K, E92Q, G118R, E138 K/A/T, G140 S/A/C, Q148 H/R/K, N155H and R263K were excluded.
Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations.
Discussion: The close proximity of the T66A/I/K variants to the viral DNA 3' end and mutation N155H, could sterically hamper viral DNA binding and/or metal ion coordination with DTG.
Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding.
Introduction: On the other hand, EVG specific resistance pathways involve IN mutations T66I/A/K, E92Q/G and S147G pathways.
Table: T66K
Integrase strand transfer inhibitor (INSTI)-resistance mutations for the surveillance of transmitted HIV-1 drug resistance.
PMID: 31617907
2020
The Journal of antimicrobial chemotherapy
Abstract: Among the 29 relatively common INSTI-selected mutations, 24 emerged as candidates for inclusion on a list of INSTI surveillance drug-resistance mutations: T66A/I/K, E92G/Q, G118R, F121Y, E138A/K/T, G140A/C/S, Y143C/H/R/S, S147G, Q148H/R/K, N155H, S230R and R263K.
Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy.
PMID: 32106437
2020
International journal of molecular sciences
Discussion: T66K reduced susceptibility to EVG by 40-fold, reduced susceptibility to RAL by 10-fold, and reduced susceptibility to DTG by 2- to 3-fold.
Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors.
PMID: 32974383
2020
Frontiers in molecular biosciences
Conclusion: Possibly, other mutations that introduce long or positively charged side chains near the ions can cause resistance by a similar mechanism of Mg2+ ion pair disruption, for instance, in the mutants T66KI.
Result: The T66I mutant could displace the ion through the introduction of an apolar and longer chain, and the T66K mutant could cause ion displacement through the introduction of a positively charged longer chain close to the divalent cation.
Result: We believe that the resistance mechanisms of T66K and T66I could occur for similar events of ion displacement.
HIV mutation literature information.
PMID: 
2022
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