ArticleJournal of virology2008
Analysis of natural sequence variation and covariation in human immunodeficiency virus type 1 integrase.
Article in Journal of virology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Specialized DNA Structures Act as Genomic Beacons for Integration by Evolutionarily Diverse Retroviruses.Viruses · 2023Pooled it
- Analysis of low-frequency mutations associated with drug resistance to raltegravir before antiretroviral treatment.Antimicrobial agents and chemotherapy · 2011Trial
- New antiretroviral inhibitors and HIV-1 drug resistance: more focus on 90% HIV-1 isolates?FEMS microbiology reviews · 2023Review
- A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing.Viruses · 2021Article
- An Evolutionary Model-Based Approach To Quantify the Genetic Barrier to Drug Resistance in Fast-Evolving Viruses and Its Application to HIV-1 Subtypes and Integrase Inhibitors.Antimicrobial agents and chemotherapy · 2019Article
- Resistance Analysis of Bictegravir-Emtricitabine-Tenofovir Alafenamide in HIV-1 Treatment-Naive Patients through 48 Weeks.Antimicrobial agents and chemotherapy · 2019Article
- Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors.Virology journal · 2017Article
- Evolutionary Analysis of HIV-1 Pol Proteins Reveals Representative Residues for Viral Subtype Differentiation.Frontiers in microbiology · 2017Article
- Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome.PloS one · 2017Article
- Prevalent polymorphisms in wild-type HIV-1 integrase are unlikely to engender drug resistance to dolutegravir (S/GSK1349572).Antimicrobial agents and chemotherapy · 2013Article
- Consensus HIV-1 FSU-A integrase gene variants electroporated into mice induce polyfunctional antigen-specific CD4+ and CD8+ T cells.PloS one · 2013Article
- Study of genotypic and phenotypic HIV-1 dynamics of integrase mutations during raltegravir treatment: a refined analysis by ultra-deep 454 pyrosequencing.The Journal of infectious diseases · 2012Article
- Switching between raltegravir resistance pathways analyzed by deep sequencing.AIDS (London, England) · 2011Article
- Patterns of resistance development with integrase inhibitors in HIV.Infection and drug resistance · 2011Article
- HIV-1 integrase sequence variability in antiretroviral naïve patients and in triple-class experienced patients subsequently treated with raltegravir.AIDS research and human retroviruses · 2010Article
- Subtype-associated differences in HIV-1 reverse transcription affect the viral replication.Retrovirology · 2010Article
- Secondary integrase resistance mutations found in HIV-1 minority quasispecies in integrase therapy-naive patients have little or no effect on susceptibility to integrase inhibitors.Antimicrobial agents and chemotherapy · 2010Article
- Raltegravir: The evidence of its therapeutic value in HIV-1 infection.Core evidence · 2010Article
- A dynamic model of HIV integrase inhibition and drug resistance.Journal of molecular biology · 2010Article
- HIV resistance to raltegravir.European journal of medical research · 2009Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human immunodeficiency virus type 1 (HIV-1) integrase inhibitors are in clinical trials, and raltegravir and elvitegravir are likely to be the first licensed drugs of this novel class of HIV antivirals. Understanding resistance to these inhibitors is important to maximize their efficacy. It has been shown that natural variation and covariation provide valuable insights into the development of resistance for established HIV inhibitors. Therefore, we have undertaken a study to fully characterize natural polymorphisms and amino acid covariation within an inhibitor-naïve sequence set spanning all defined HIV-1 subtypes. Inter- and intrasubtype variation was greatest in a 50-amino-acid segment of HIV-1 integrase incorporating the catalytic aspartic acid codon 116, suggesting that polymorphisms affect inhibitor binding and pathways to resistance. The critical mutations that determine the resistance pathways to raltegravir and elvitegravir (N155H, Q148K/R/H, and E92Q) were either rare or absent from the 1,165-sequence data set. However, 25 out of 41 mutations associated with integrase inhibitor resistance were present. These mutations were not subtype associated and were more prevalent in the subtypes that had been sampled frequently within the database. A novel modification of the Jaccard index was used to analyze amino acid covariation within HIV-1 integrase. A network of 10 covarying resistance-associated mutations was elucidated, along with a further 15 previously undescribed mutations that covaried with at least two of the resistance positions. The validation of covariation as a predictive tool will be dependent on monitoring the evolution of HIV-1 integrase under drug selection pressure.
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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.