Comparable In Vitro Activities of Second-Generation HIV-1 Integrase Strand Transfer Inhibitors (INSTIs) on HIV-1 Clinical Isolates with INSTI Resistance Mutations.
PMID: 31611362
2019
Antimicrobial agents and chemotherapy
Abstract: In this study, DTG, BIC, and CAB demonstrated a comparable activity on a panel of INSTI-resistant strains isolated from patients exposed to RAL, EVG, and/or DTG, with a significantly reduced susceptibility only with the pathway Q148H/K/R plus one to two additional INSTI mutations.
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: INSTI DRM Q148H/K/R declined from 39.3% (2010) to 13.8% (2017).
Prevalence and clinical impact of minority resistant variants in patients failing an integrase inhibitor-based regimen by ultra-deep sequencing.
PMID: 29873733
2018
The Journal of antimicrobial chemotherapy
Abstract: Among 53 patients harbouring at least one resistance mutation detected by both techniques, the most dominant INSTI resistance mutations were N155H (45%), Q148H/K/R (23%), T97A (19%) and Y143C (11%).
Long-term efficacy of dolutegravir in treatment-experienced subjects failing therapy with HIV-1 integrase strand inhibitor-resistant virus.
PMID: 29077927
2018
The Journal of antimicrobial chemotherapy
Abstract: A higher risk of VF was independently associated with baseline viral load >100000 copies/mL (adjusted HR = 4.73, 95% CI = 1.33-16.78, P = 0.016) and with >=1 INSTI mutations plus Q148H/K/R/N and the G140S/A/C as compared with other subjects (adjusted HR = 4.18, 95% CI = 1.32-13.23, P = 0.015).
Ex-vivo antiretroviral potency of newer integrase strand transfer inhibitors cabotegravir and bictegravir in HIV type 1 non-B subtypes.
Result: Five patients (21%) with multiple mutations (Q148QR+N155H, G140A+Q148R, E138K+G140S+Q148R, E138K+G140A+ S147SG+Q148K and G140S+Q148H+N155H) were predicted to have high-level cross resistance to DTG, CAB, and BIC, although no phenotypic assessment has confirmed this observation.
Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance.
Result: 1e) mutations from all three major resistance pathways including double mutants with secondary mutations were observed with G140S + Q148H being the most frequently occurring double mutant.
Result: N155H was found in 14.4%, of the population, Q148H in 7.5% of which approximately half (4.1%) in combination with G140S and the remainder in combination with E157D.
Result: Population sequencing (sample 457 days after initiation of raltegravir) demonstrated that virus with integrase substitutions G140S + Q148H completely dominated the viral popu
Novel secondary mutations C56S and G149A confer resistance to HIV-1 integrase strand transfer inhibitors.
Abstract: During passage with Q148H virus, G140S arose by day 14, followed by G149A and C56S.
Abstract: Signature mutant viruses G140S/Q148H in which C56S and G149A were added acquired further INSTI resistance in conjunction with diminished integration activity, which yielded slower growth under drug-free conditions.
Accumulation of Multiple Mutations In Vivo Confers Cross-Resistance to New and Existing Integrase Inhibitors.
PMID: 30010985
2018
The Journal of infectious diseases
Abstract: The combination of major integrase inhibitor substitutions G140S/Q148H has been shown to confer high-level resistance to the approved integrase inhibitors raltegravir (RAL) and elvitegravir (EVG) but not necessarily dolutegravir (DTG).
Abstract: We assayed recombinant viruses made from patient-derived RNA extracts for resistance phenotype for a panel of viruses containing G140S/Q148H with additional accessory substitutions.
Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir.
PMID: 30568974
2018
Open forum infectious diseases
Conclusion: In November 2014, a PhenoSense Integrase GT assay detected DRMs to NRTI, NNRTI, PI, and the INSTI-associated mutations E138T, G140S, and Q148H.
Conclusion: Interpretation of cumulative genotypic information (Standford/ANRS algorithms) indicated high-level
Introduction: T97A is an accessory mutation frequently co-selected with additional drug resistance mutations (DRMs) including Q148H and G140S in individuals failing raltegravir (RAL) or elvitegravir (EVG) therapy and contributes substantially to resistance to these first-generation INSTIs.
Durable suppression of HIV-1 with resistance mutations to integrase inhibitors by dolutegravir following drug washout.
Abstract: DESIGN AND METHODS: MT-2 cells infected with wild-type, R263K or G140S/Q148H HIV-1 clones were treated with DTG, RAL or EVG for 3 days.
Abstract: Now, we performed DTG, EVG and RAL washout experiments to compare the recovery of viral integration and production of 2-long terminal repeat (LTR) circles using wild-type HIV-1 clones, R263K viruses with low-level resistance to DTG and viruses with G140S/Q148H mutations showing cross-resistance against all currently approved INSTIs.
Abstract: With the G140S/Q148H virus, levels of integration were not significantly affected by the presence o
HIV mutation literature information.
PMID: 
2019
Antimicrobial agents and chemotherapy
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