ArticleAntimicrobial agents and chemotherapy2010
Impact of Y143 HIV-1 integrase mutations on resistance to raltegravir in vitro and in vivo.
Article in Antimicrobial agents and chemotherapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
42 citing papers in PubMed, 74 citations in OpenAlex.
- Efficacy and safety of raltegravir for treatment of HIV for 5 years in the BENCHMRK studies: final results of two randomised, placebo-controlled trials.The Lancet. Infectious diseases · 2013Trial
- Analysis of low-frequency mutations associated with drug resistance to raltegravir before antiretroviral treatment.Antimicrobial agents and chemotherapy · 2011Trial
- Review
- Article
- Coevolved Multidrug-Resistant HIV-1 Protease and Reverse Transcriptase Influences Integrase Drug Susceptibility and Replication Fitness.Pathogens (Basel, Switzerland) · 2021Article
- Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir.Retrovirology · 2018Article
- Probing Resistance Mutations in Retroviral Integrases by Direct Measurement of Dolutegravir Fluorescence.Scientific reports · 2017Article
- Article
- HIV drug resistance against strand transfer integrase inhibitors.Retrovirology · 2017Review
- Synthesis and Anti-HIV-1 Activity Evaluation for Novel 3a,6a-Dihydro-1H-pyrrolo[3,4-c]pyrazole-4,6-dione Derivatives.Molecules (Basel, Switzerland) · 2016Article
- Selectivity for strand-transfer over 3'-processing and susceptibility to clinical resistance of HIV-1 integrase inhibitors are driven by key enzyme-DNA interactions in the active site.Nucleic acids research · 2016Article
- Opposite transcriptional regulation of integrated vs unintegrated HIV genomes by the NF-κB pathway.Scientific reports · 2016Article
- Different Pathways Leading to Integrase Inhibitors Resistance.Frontiers in microbiology · 2016Review
- Dolutegravir maintains a durable effect against HIV replication in tissue culture even after drug washout.The Journal of antimicrobial chemotherapy · 2015Article
- Simian-tropic HIV as a model to study drug resistance against integrase inhibitors.Antimicrobial agents and chemotherapy · 2015Article
- Identification of highly conserved residues involved in inhibition of HIV-1 RNase H function by Diketo acid derivatives.Antimicrobial agents and chemotherapy · 2014Article
- Effect of HIV-1 integrase resistance mutations when introduced into SIVmac239 on susceptibility to integrase strand transfer inhibitors.Journal of virology · 2014Article
- 4-amino-1-hydroxy-2-oxo-1,8-naphthyridine-containing compounds having high potency against raltegravir-resistant integrase mutants of HIV-1.Journal of medicinal chemistry · 2014Article
- Bicyclic 1-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxamide-containing HIV-1 integrase inhibitors having high antiviral potency against cells harboring raltegravir-resistant integrase mutants.Journal of medicinal chemistry · 2014Article
- Multiple genetic pathways involving amino acid position 143 of HIV-1 integrase are preferentially associated with specific secondary amino acid substitutions and confer resistance to raltegravir and cross-resistance to elvitegravir.Antimicrobial agents and chemotherapy · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Integrase (IN), the HIV-1 enzyme responsible for the integration of the viral genome into the chromosomes of infected cells, is the target of the recently approved antiviral raltegravir (RAL). Despite this drug's activity against viruses resistant to other antiretrovirals, failures of raltegravir therapy were observed, in association with the emergence of resistance due to mutations in the integrase coding region. Two pathways involving primary mutations on residues N155 and Q148 have been characterized. It was suggested that mutations at residue Y143 might constitute a third primary pathway for resistance. The aims of this study were to investigate the susceptibility of HIV-1 Y143R/C mutants to raltegravir and to determine the effects of these mutations on the IN-mediated reactions. Our observations demonstrate that Y143R/C mutants are strongly impaired for both of these activities in vitro. However, Y143R/C activity can be kinetically restored, thereby reproducing the effect of the secondary G140S mutation that rescues the defect associated with the Q148R/H mutants. A molecular modeling study confirmed that Y143R/C mutations play a role similar to that determined for Q148R/H mutations. In the viral replicative context, this defect leads to a partial block of integration responsible for a weak replicative capacity. Nevertheless, the Y143 mutant presented a high level of resistance to raltegravir. Furthermore, the 50% effective concentration (EC(50)) determined for Y143R/C mutants was significantly higher than that obtained with G140S/Q148R mutants. Altogether our results not only show that the mutation at position Y143 is one of the mechanisms conferring resistance to RAL but also explain the delayed emergence of this mutation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.