literature

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: 26404079 2016 The Journal of antimicrobial chemotherapy

Abstract: Among the seven major integrase mutations (T66I, E92Q, G140S, Y143C/H/R, S147G, Q148H/K/R and N155H), only one strain harbouring the Q148R mutation was detected.

Drug Susceptibility and Viral Fitness of HIV-1 with Integrase Strand Transfer Inhibitor Resistance Substitution Q148R or N155H in Combination with Nucleoside/Nucleotide Reverse Transcriptase Inhibitor Resistance Substitutions.

PMID: 26574015 2016 Antimicrobial agents and chemotherapy

Abstract: In clinical trials of coformulated elvitegravir (EVG), cobicistat (COBI), emtricitabine (FTC), and tenofovir disoproxil fumarate (TDF), emergent drug resistance predominantly involved the FTC resistance substitution M184V/I in reverse transcriptase (RT), with or without the tenofovir (TFV) resistance substitution K65R, accompanied by a primary EVG resistance substitution (E92Q, N155H, or Q148R) in integrase (IN).

Abstract: We previously reported that the RT-K65R, RT-M184V, and IN-

Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses.

PMID: 27130466 2016 Retrovirology

Introduction: The absence of compensatory secondary mutations for R263K is also consistent with the observation that many major RAL- and EVG-resistance substitutions such as G140S, Q148R, E92Q, N155H

Discussion: Compared to WT virus, the R263K substitution as well as some other major mutations E92Q, Q148R and N155H, reported in the RAL- and/or EVG-resistance pathways, can emerge from a single nucleotide change in most HIV-1 strains.

Discussion: For example, N155H virus caused sixfold and fivefold decreases in susceptibility to RAL and EVG and E92Q conferred more than a 50-fold decrease in EVG susceptibility.

Prevalence of Integrase Strand Transfer Inhibitors (INSTI) Resistance Mutations in Taiwan.

PMID: 27779200 2016 Scientific reports

Method: Besides these three major mutations, the integrase substitutions with a Stanford HIVdb score 10 to at least one INSTI were included, such as H51Y, T66A/I/K, L74M, E92G/Q/V, Q95K, T97A, F121Y, E138A/K, G140S/C/A, Y143G/K/S/A, P145S, Q146P, S147G, V151A/L, S153F/Y, N155S/T,

Therapy-Emergent Drug Resistance to Integrase Strand Transfer Inhibitors in HIV-1 Patients: A Subgroup Meta-Analysis of Clinical Trials.

PMID: 27532886 2016 PloS one

Abstract: The resistance of DTG is mainly shown in 13 integrase mutations (including T97T/A, E138E/D, V151V/I, N155H, Q148, Y143C/H/R, T66A and E92Q).

Abstract: The ten major integrase mutations (including N155H, Y143C/R, Q148H/R, Y143Y/H, L74L/M, E92Q, E138E/A, Y143C, Q148Q and

Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence.

PMID: 26198244 2015 Viruses

Introduction: Under such circumstances, extensive genotypic characterisation of resistant strains from two large clinical studies, i.e., Studies 102 and 103, revealed the emergence of the T66I, E92Q, T97A, Q148R and N155H resistance mutations in integrase, mostly in combination with the M184I/V substitutions in RT.

Table: E92E/Q

Table: E92Q

Dolutegravir-Selected HIV-1 Containing the N155H and R263K Resistance Substitutions Does Not Acquire Additional Compensatory Mutations under Drug Pressure That Lead to Higher-Level Resistance and Increased Replicative Capacity.

PMID: 26246578 2015 Journal of virology

Abstract: To this end, each of the L74M, E92Q, T97A, E157Q, and G163R substitutions were introduced into NL4.3 subtype B HIV-1 vectors harboring N155H and R263K in tandem [termed NL4.3IN(N155H/R263K)].

Abstract: We found that the addition of T97A, E157Q, or G163R somewhat improved the affinity of INN155H/R263K for its target DNA substrate, while the presence of L74M or E92Q had a negative effect on th

Characterization of the Drug Resistance Profiles of Integrase Strand Transfer Inhibitors in Simian Immunodeficiency Virus SIVmac239.

PMID: 26378179 2015 Journal of virology

Abstract: RAL and EVG showed reduced activity against both viruses and against enzymes containing Q148R, E92Q Y143R, and G140S Q148R.

Abstract: To study this at a biochemical level, purified recombinant SIVmac239 wild-type (WT) and E92Q, T97A, G118R, Y143R, Q148R, N155H, R263K, E92Q T97A, E92Q Y143R, R263K H51Y, and

PMID: 25927004 2015 Acta naturae

Introduction: We characterized the catalytic activity of INA and its variants containing two major combinations of RALand EVG-resistance mutations: E92Q, V151I, N155H, G163R, L74M (mutant 1), and Q148K, E138K, G140S (mutant 2) .