literature

HIV mutation literature information.

Ex-vivo antiretroviral potency of newer integrase strand transfer inhibitors cabotegravir and bictegravir in HIV type 1 non-B subtypes.

PMID: 29239896 2018 AIDS (London, England)

Result: In addition, 17 of 270 (6.3%) patients had at least one major accessory DRM: T97A (n=3), E157Q (n=12), or A128T (n=2).

Result: The A128T is a non-polymorphic mutation selected in vitro by EVG, but does not appear to reduce INSTI susceptibility ex vivo.

Performance of Celera RUO integrase resistance assay across multiple HIV-1 subtypes.

PMID: 27993614 2017 Journal of virological methods

Result: Differences in mutations were observed at three codons in integrase associated with integrase drug resistance (A128T, T97A and V151I).

Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors.

PMID: 29137637 2017 Virology journal

Method: 26, September 2016), HIV-GRADE (http://www.hiv-grade.de, version January 16, 2017), and Rega (https://rega.kuleuven.be/cev/avd/software/rega-algorithm, v9.0.1, October 29, 2013) were considered: A49G, H51Y, V54I, L68IV, L74I, E92V, Q95K, H114Y, G118R, S119R, T124A, A128T, E138T, G140C, Y143AGS, P145S, Q146IKLPR, Q148EG,

PMID: 28891788 2017 HIV clinical trials

Method: Secondary INSTI-R substitutions assessed were M50I, H51Y, L68I/V, V72A/N/T, L74M, Q95K/R, G118R, S119P/R/T, F121C/Y, A128T, E138A/K, G140A/C/S, P145S, Q146I/K/L/P/R, V151A/L, S153A/F/Y, E157K/Q, G163K/R,

Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome.

PMID: 28212411 2017 PloS one

Result: Some secondary integrase mutations associated with resistance to EVG and/or RAL were detected as natural integrase polymorphisms, most often at very low frequencies (0.5-1%: V72T, L74M, A128T, and G163R) with few exceptions (19%: M50I; 59%: S119P/G/T/R; and 3.8%: E157Q).

Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile.

PMID: 27645238 2016 Antimicrobial agents and chemotherapy

Figure: Primary INSTI resistance mutations are T66I/A/K, E92Q/G, T97A, Y143C/H/R, S147G, Q148H/K/R, and N155H, and other INSTI resistance mutations are H51Y, L68I/V, V72A/N/T, L74M, Q95K/R, F121C/Y, A128T, E138A/K, G140A/C/S, P145S,

PMID: 27568085 2016 Bioorganic & medicinal chemistry letters

Abstract: The most potent of these compounds displayed good activity in the LEDGF/p75 dependent integration assay (IC50=4.5muM) and, as predicted based on the geometry of the five- versus six-membered ring, retained activity against the A128T IN mutant that confers resistance to many quinoline-based ALLINIs.

Introduction: Although these compounds and many others have shown promising inhibitory activity, various resistance mutations, including the A128T IN mutation, have been observed for many of the reported quinoline-based ALLINIs.

Introduction: As predicted by the computational docking model, the five-membered indole ring structure of 5c mitigates the repulsion induced by the A128T mutation by tilting the aromatic ring away from the 128 residue of subunit 1, thus maintaining similar activities agai

Development and validation of a cell-based assay system to assess human immunodeficiency virus type 1 integrase multimerization.

PMID: 27474494 2016 Journal of virological methods

Abstract: An IN's substitution, A128T, associated with viral resistance to NCINIs, decreased the NCINI-induced increase of fluorescence, suggesting that A128T reduces the potential for Discussion: When the potential utility of the current BiFC-IN system was further examined using the NCINIs, significant IN over-multimerization in the BiFC-IN system, well associated with the EC50 value of each NCINI, was observed to have occurred for all 3 NCINIs, while the A128T substitution-carrying IN showed less multimerization, demonstrating that the BiFC-IN system is useful for evaluating IN over-multimerization caused by NCINIs.

The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase.

PMID: 25421939 2014 Retrovirology

Introduction: Consequently, BI-1001 was unable to promote aberrant multimerization of recombinant A128T IN, whereas it maintained its ability to inhibit IN-LEDGF/p75 binding in vitro.

Introduction: Interestingly, crystallographic studies have revealed that BI-1001 is still able to bind A128T IN CCD by maintaining all hydrogen bonding interactions, but that the quinoline ring bridging the two IN subunits was slightly shifted compared with the wild type (WT) protein.

Introduction: Of these, the A128T IN substitution was the most prevalent mutation with HIV-1NL4-3(A128T IN) displaying marked resistance to respective

A critical role of the C-terminal segment for allosteric inhibitor-induced aberrant multimerization of HIV-1 integrase.

PMID: 25118283 2014 The Journal of biological chemistry

Abstract: Here, we used mass spectrometry-based protein footprinting to monitor surface topology changes in full-length WT and the drug-resistant A128T mutant INs in the presence of ALLINI-2.

Abstract: These experiments have identified protein-protein interactions that extend beyond the direct inhibitor binding site and which lead to aberrant multimerization of WT but not A128T IN.

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