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.
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: T66A and T66I reduce EVG susceptibility, respectively, by 5-fold and 10-fold.
Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa.
Introduction: On the other hand, EVG specific resistance pathways involve IN mutations T66I/A/K, E92Q/G and S147G pathways.
Table: T66I
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.
Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting.
Abstract: Primary mutations (Y143C, N155H, T66I, G118R, E138K) conferring high level resistance to raltegravir were detected in only three patients.
Result: Among patients with M184V mutation, two had mutations at position 138 of reverse transcriptase that is associated with low-level resistance to the NNRTI, rilpivirine, and three had major mutations (Y143C, N155H, T66I, G118R, E138K) conferring high level resistance to RAL (Table 2).
Table: T66I
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: This hypothesis is also supported by the fact that N155H and T66I have similar EC50 profiles.
Result: We believe that the resistance mechanisms of T66K and T66I could occur for similar events of ion displacement.
Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I.
PMID: 31430369
2019
The Journal of antimicrobial chemotherapy
Method: Primary INSTI resistance (-R) substitutions were T66I/A/K, E92Q/G, T97A, F121Y, Y143R/H/C, S147G, Q148H/K/R, N155H/S and R263K in IN.
Trends in HIV-1 Drug Resistance Mutations from a U.S. Reference Laboratory from 2006 to 2017.
PMID: 31169022
2019
AIDS research and human retroviruses
Abstract: Prevalence of elvitegravir-associated DRMs T66A/I/K, E92Q, S147G, and the dolutegravir-associated DRM R263K increased.
HIV mutation literature information.
PMID: 
2021
BMC infectious diseases
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