ArticleAntimicrobial agents and chemotherapy2008
Mutations associated with failure of raltegravir treatment affect integrase sensitivity to the inhibitor in vitro.
Article in Antimicrobial agents and chemotherapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01381328 (GePheRal), which is not on this map. Cited by 115 papers, 1 of them a synthesis that pooled it.
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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.
GePheRal: Clinical Validation of the Genotypic Diagnosis of Hiv-1 Resistance to Raltegravir by Parallel Analysis of the Genotype and Phenotype Profiles of Resistance
Who cites it
115 citing papers in PubMed, 1 synthesis or guideline pooled it, 279 citations in OpenAlex.
- Current ARTs, Virologic Failure, and Implications for AIDS Management: A Systematic Review.Viruses · 2023Pooled it
- Analysis of low-frequency mutations associated with drug resistance to raltegravir before antiretroviral treatment.Antimicrobial agents and chemotherapy · 2011Trial
- Article
- Review
- Article
- Structure of a HIV-1 IN-Allosteric inhibitor complex at 2.93 Å resolution: Routes to inhibitor optimization.PLoS pathogens · 2023Article
- Review
- 2022 update of the drug resistance mutations in HIV-1.Topics in antiviral medicine · 2022Article
- HIV-1 non-B resistance mutations and natural polymorphisms to integrase strand transfer inhibitors in recently diagnosed patients in Gabon, Central Africa.The Journal of antimicrobial chemotherapy · 2022Article
- Article
- HIV-1 Integrase Inhibitors with Modifications That Affect Their Potencies against Drug Resistant Integrase Mutants.ACS infectious diseases · 2021Article
- Review
- Structural Insights to Human Immunodeficiency Virus (HIV-1) Targets and Their Inhibition.Advances in experimental medicine and biology · 2021Article
- Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naïve HIV Patients in Southeast China.Drug design, development and therapy · 2021Article
- Retroviral integrase: Structure, mechanism, and inhibition.The Enzymes · 2021Article
- HIV-1 Integrase Inhibitors That Are Active against Drug-Resistant Integrase Mutants.Antimicrobial agents and chemotherapy · 2020Article
- Non-Nucleoside Reverse Transcriptase Inhibitors Join Forces with Integrase Inhibitors to Combat HIV.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy.International journal of molecular sciences · 2020Article
- Recent Advances in the Development of Integrase Inhibitors for HIV Treatment.Current HIV/AIDS reports · 2020Review
- 2019 update of the drug resistance mutations in HIV-1.Topics in antiviral medicine · 2019Article
55 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Raltegravir (MK-0518) is a potent inhibitor of human immunodeficiency virus (HIV) integrase and is clinically effective against viruses resistant to other classes of antiretroviral agents. However, it can select mutations in the HIV integrase gene. Nine heavily pretreated patients who received salvage therapy including raltegravir and who subsequently developed virological failure under raltegravir therapy were studied. For each patient, the sequences of the integrase-coding region were determined and compared to that at the beginning of the treatment. Four different mutation profiles were identified in these nine patients: E92Q, G140S Q148H, N155H, and E157Q mutations. For four patients, each harboring a different profile, the wild-type and mutated integrases were produced, purified, and assayed in vitro. All the mutations identified altered the activities of integrase protein: both 3' processing and strand transfer activities were moderately affected in the E92Q mutant; strand transfer was markedly impaired in the N155H mutant; both activities were strongly impaired in the G140S Q148H mutant; and the E157Q mutant was almost completely inactive. The sensitivities of wild-type and mutant integrases to raltegravir were compared. The E92Q and G140S Q148H profiles were each associated with a 7- to 8-fold decrease in sensitivity, and the N155H mutant was more than 14-fold less sensitive to raltegravir. At least four genetic profiles (E92Q, G140S Q148H, N155H, and E157Q) can be associated with in vivo treatment failure and resistance to raltegravir. These mutations led to strong impairment of enzymes in vitro in the absence of raltegravir: strand transfer activity was affected, and in some cases 3' processing was also impaired.
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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.