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, Y143R/C/H, S147G, Q148H/R/K, N155H, and R263K) were assessed to explore the genetic barrier to DTG.
Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials.
PMID: 34897227
2022
Journal of acquired immune deficiency syndromes (1999)
Introduction: Primary INSTI drug resistance reported in surveillance studies are mainly substitutions that cause resistance to RAL and EVG (T66A/I, E92Q, Y143C/H/R, S147G, Q148H/K/R, and N155H pathways) and R263K, which confers low-level reduced susceptibility to EVG, DTG, and bictegravir (BIC).
Table: T66I/A
Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study.
PMID: 34694877
2022
Antimicrobial agents and chemotherapy
Table: T66A/I
Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations.
Figure: b T66A HIV-1 CRF02_AG IN showing in total four contacts formed between DTG and one IN residue, one DNA nucleotide and two MG ions.
Discussion: Abraham et al., 2013, showed that the T66A mutant occurs within the two distal sheet from the DDE
Discussion: The variant T66A which is normally selected by EVG treatment, was detected in 0.3% of our sequence cohort.
Discussion: This was further explored by performing interaction analysis between the drug DTG and energy minimized structures of the WT and mutants T66A, T97A, Q148H, N155H, E157Q, R263K and D232N.
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, Result: The four individuals failing DTG cART but with no documented prior exposure to RAL, their selected DRMs were E138K, G140A, Q148K, A128T; G118R, E138K; N155ND and T66A, G118R, E138EAKT Figure 3.
Increased acquired protease inhibitor drug resistance mutations in minor HIV-1 quasispecies from infected patients suspected of failing on national second-line therapy in South Africa.
Discussion: Previous studies on HIV-1C have shown major INI mutations at baseline in less than 5% of patients from Ethiopia (T66I, E138K, Q148R, and Q148H) and South Africa (Q148H, T66S, E92G, S147G, T66A, Y143YF and Y143H).
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.
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: T66A
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
Result: The proporti
Result: Two INSTIs major RAMs were identified in two database samples: T66A in 1 (0.47%) HIV-1 group M/O recombinant sample isolated in 1997 from a 29 years old ART-naive Cameroonian female (GenBank accession number: AJ239083); and N155K in 1 (0.47%) CRF36_cpx sample isolated in 2000 from a 19 years old female in Cameroon (GenBank accession number: EF087995) (Table 3).
Discussion: T66A and T66I reduce EVG susceptibility, respectively, by 5-fold and 10-fold.
Discussion: No INSTIs major RAMs were present in cohort samples, and only 2 database samples had INSTIs major RAMs: T66A in a group M/O recombinant and N155K in a CRF36_cpx sample.
HIV mutation literature information.
PMID: 
2022
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