[Resistance profile and genetic barrier of dolutegravir].
PMID: 25858608
2015
Enfermedades infecciosas y microbiologia clinica
Abstract: Dolutegravir displays in vitro activity against mutant HIV-1 harboring any isolated resistance mutations selected during failures to raltegravir or elvitegravir (Y143C/H/, N155H, Q148H/K/R, E92G/Q, T66A/I/K, T97A, E138A/K, G140A/S).
Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study.
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) .
Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence.
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.
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
Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades.
PMID: 26311843
2015
The Journal of antimicrobial chemotherapy
Introduction: Three genotypic resistance pathways were identified: N155H (+-E92Q), Q148H/R/K (+-G140S) and Y143R (+-T97A).
Method: Major RAMs comprised T66A/I/K, E92Q/G/V, F121Y, Table: E92Q
Discussion: Consistent with available data, there was a strong preferential association of N155H with E92Q, Y143H/R/C with T97A, and G140S/A with Q148H/R/K.
Characterization of the Drug Resistance Profiles of Integrase Strand Transfer Inhibitors in Simian Immunodeficiency Virus SIVmac239.
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: 26626277
2015
Journal of translational medicine
Abstract: Neither major resistance-associated IN mutations (T66I/A/K, E92Q/G, T97A, Y143HCR, S147G, Q148H/R/K, and N155H) nor silent mutations known to change the genetic barrier were observed.
Conclusion: None of the previously reported major mutations (T66AIK, E92Q, Y143RCH, S147G, Q148HRK and N155H) associated with resistance to INIs were observed in HIV-1C Ethiopian isolates, indicating that
Resistance to HIV integrase strand transfer inhibitors among clinical specimens in the United States, 2009-2012.
Abstract: Major integrase mutations included T66AIK, E92QV, F121Y, Y143CHR, S147G, Q148HKR, and N155H; multiple accessory mutations were also assessed.
HIV-1-infected patients with advanced disease failing a raltegravir-containing salvage regimen in Sao Paulo, Brazil.
PMID: 24359837
2014
International journal of antimicrobial agents
Abstract: At failure, major RAL resistance mutations included Q148H/R/K (21/47; 45%), N155H (14/47; 30%), Y143R/H/C (3/47; 6%) and E92Q (1/47; 2%).
Genotypic resistance profiles of HIV-2-treated patients in West Africa.
Result: Integrase region was sequenced in the patient in virological failure when receiving raltegravir-based regimen, showing the major resistance mutation N155H associated with the secondary mutations E92Q and T97A.