ArticleRetrovirology2018
Efficacies of Cabotegravir and Bictegravir against drug-resistant HIV-1 integrase mutants.
Article in Retrovirology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 111 citations in OpenAlex.
- A systematic review of the genetic mechanisms of dolutegravir resistance.The Journal of antimicrobial chemotherapy · 2019Pooled it
- Trial
- Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on theAntimicrobial agents and chemotherapy · 2022Trial
- Targeting Human Immunodeficiency Virus Integrase Beyond the Active Site: The Discovery and Development of Allosteric Integrase Inhibitors.ChemMedChem · 2026Review
- Non-integrase mechanisms for dolutegravir resistance.Retrovirology · 2026Review
- Review
- An ultra-long-acting dimeric bictegravir prodrug defined by a short pharmacokinetic tail.Nature communications · 2026Article
- Design and Evaluation of Next-Generation HIV Genotyping for Detection of Resistance Mutations to 28 Antiretroviral Drugs Across 5 Major Classes Including Lenacapavir.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2025Article
- Article
- Pi-pi stacking interactions with viral DNA contribute to the potency of naphthyridine-based HIV-1 integrase inhibitors.NAR molecular medicine · 2025Article
- Article
- HIV-1 Integrase T218I/S Polymorphisms Do Not Reduce HIV-1 Integrase Inhibitors' Phenotypic Susceptibility.AIDS research and human retroviruses · 2025Article
- HIV-1 diversity and pre-treatment drug resistance in the era of integrase inhibitor among newly diagnosed ART-naïve adult patients in Luanda, Angola.Scientific reports · 2024Article
- Design, synthesis and biological evaluation of indole-2-carboxylic acid derivatives as novel HIV-1 integrase strand transfer inhibitors.RSC advances · 2024Article
- Article
- The Discovery of Indole-2-carboxylic Acid Derivatives as Novel HIV-1 Integrase Strand Transfer Inhibitors.Molecules (Basel, Switzerland) · 2023Article
- Review
- Mechanisms of HIV-1 integrase resistance to dolutegravir and potent inhibition of drug-resistant variants.Science advances · 2023Article
- Long Dissociation of Bictegravir from HIV-1 Integrase-DNA Complexes.Antimicrobial agents and chemotherapy · 2023Article
- A computational overview of integrase strand transfer inhibitors (INSTIs) against emerging and evolving drug-resistant HIV-1 integrase mutants.Archives of microbiology · 2023Review
9 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
4 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundIntegrase strand transfer inhibitors (INSTIs) are the class of antiretroviral (ARV) drugs most recently approved by the FDA for the treatment of HIV-1 infections. INSTIs block the strand transfer reaction catalyzed by HIV-1 integrase (IN) and have been shown to potently inhibit infection by wild-type HIV-1. Of the three current FDA-approved INSTIs, Dolutegravir (DTG), has been the most effective, in part because treatment does not readily select for resistant mutants. However, recent studies showed that when INSTI-experienced patients are put on a DTG-salvage therapy, they have reduced response rates. Two new INSTIs, Cabotegravir (CAB) and Bictegravir (BIC), are currently in late-stage clinical trials.
resultsBoth CAB and BIC had much broader antiviral profiles than RAL and EVG against the INSTI-resistant single, double, and triple HIV-1 mutants used in this study. BIC was more effective than DTG against several INSTI-resistant mutants. Overall, in terms of their ability to inhibit a broad range of INSTI-resistant IN mutants, BIC was superior to DTG, and DTG was superior to CAB. Modeling the binding of CAB, BIC, and DTG within the active site of IN suggested that the "left side" of the INSTI pharmacophore (the side away from the viral DNA) was important in determining the ability of the compound to inhibit the IN mutants we tested.
conclusionsOf the two INSTIs in late stage clinical trials, BIC appears to be better able to inhibit the replication of a broad range of IN mutants. BIC retained potency against several of the INSTI-resistant mutants that caused a decrease in susceptibility to DTG.
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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.