ArticleJournal of virology2012
Characterization of the R263K mutation in HIV-1 integrase that confers low-level resistance to the second-generation integrase strand transfer inhibitor dolutegravir.
Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers, 1 of them a synthesis that pooled it.
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Who cites it
136 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A systematic review of the genetic mechanisms of dolutegravir resistance.The Journal of antimicrobial chemotherapy · 2019Pooled it
- Phase 2 Trial of Long-Acting Cabotegravir and VRC07-523LS for Viral Suppression in Adults With HIV-1: ACTG A5357.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026Trial
- Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study.Antimicrobial agents and chemotherapy · 2022Trial
- CRISPR/Cas9-Based Genome Editing: Understanding Differences in DNA Repair Pathways, Profiles, and Outcomes.International journal of molecular sciences · 2026Review
- Non-integrase mechanisms for dolutegravir resistance.Retrovirology · 2026Review
- Mutation-Tolerant Inhibition of HIV-1 Integrase Strand Transfer by Secondary Metabolites from the Endophytic FungusMicroorganisms · 2026Article
- Review
- Treatment-Emergent Bictegravir Resistance in a Treatment-Naive Individual With HIV Infection: A Case Report.Cureus · 2026Article
- HIV-1 and HIV-2 interaction results in reduced cell infectivity and viral replication in vitro.Virology journal · 2026Article
- Cooperation between HIV-1 integrase natural polymorphism K156N and 3'PPT mutations in dolutegravir monotherapy failure.The Journal of antimicrobial chemotherapy · 2026Article
- HIV-1 Drug Resistance Trends in the Era of Modern Antiretrovirals: 2018-2024.Open forum infectious diseases · 2025Article
- Computational and Population-Based HLA Permissiveness to HIV Drug Resistance-Associated Mutations.Pathogens (Basel, Switzerland) · 2025Article
- Pretreatment HIV Drug Resistance to Integrase Strand Transfer Inhibitors Among Newly Diagnosed HIV Individuals - China, 2018-2023.China CDC weekly · 2025Article
- The urgent need for newer drugs in routine HIV treatment in Africa: the case of Ghana.Frontiers in epidemiology · 2025Review
- HIV-1 Integrase T218I/S Polymorphisms Do Not Reduce HIV-1 Integrase Inhibitors' Phenotypic Susceptibility.AIDS research and human retroviruses · 2025Article
- Prevalence of major INSTI and HIV-1 drug resistance mutations in pre- and antiretroviral-treated patients in Indonesia.Narra J · 2024Article
- Comprehensive database of HIV mutations selected during antiretroviral in vitro passage experiments.Antiviral research · 2024Article
- Decoupling HIV-1 antiretroviral drug inhibition from plasma antibody activity to evaluate broadly neutralizing antibody therapeutics and vaccines.Cell reports. Medicine · 2024Article
- A multicompartment population PK model to predict tenofovir and emtricitabine mucosal tissue concentrations for HIV prevention.CPT: pharmacometrics & systems pharmacology · 2023Article
- Epidemiological and molecular characterization of HBV and HCV infections in HIV-1-infected inmate population in Italy: a 2017-2019 multicenter cross-sectional study.Scientific reports · 2023Article
76 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors.
Funding
Abstract
Integrase (IN) strand transfer inhibitors (INSTIs) have been developed to inhibit the ability of HIV-1 integrase to irreversibly link the reverse-transcribed viral DNA to the host genome. INSTIs have proven their high efficiency in inhibiting viral replication in vitro and in patients. However, first-generation INSTIs have only a modest genetic barrier to resistance, allowing the virus to escape these powerful drugs through several resistance pathways. Second-generation INSTIs, such as dolutegravir (DTG, S/GSK1349572), have been reported to have a higher resistance barrier, and no novel drug resistance mutation has yet been described for this drug. Therefore, we performed in vitro selection experiments with DTG using viruses of subtypes B, C, and A/G and showed that the most common mutation to emerge was R263K. Further analysis by site-directed mutagenesis showed that R263K does confer low-level resistance to DTG and decreased integration in cell culture without altering reverse transcription. Biochemical cell-free assays performed with purified IN enzyme containing R263K confirmed the absence of major resistance against DTG and showed a slight decrease in 3' processing and strand transfer activities compared to the wild type. Structural modeling suggested and in vitro IN-DNA binding assays show that the R263K mutation affects IN-DNA interactions.
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