ArticleProceedings of the National Academy of Sciences of the United States of America2002
HIV-1 escape from a small molecule, CCR5-specific entry inhibitor does not involve CXCR4 use.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers.
What it found
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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
121 citing papers in PubMed, 304 citations in OpenAlex.
- HIV-1 clinical isolates resistant to CCR5 antagonists exhibit delayed entry kinetics that are corrected in the presence of drug.Journal of virology · 2012Trial
- Pharmacokinetics and pharmacodynamics of TBR-652, a novel CCR5 antagonist, in HIV-1-infected, antiretroviral treatment-experienced, CCR5 antagonist-naïve patients.Antimicrobial agents and chemotherapy · 2011Trial
- Virologic failure in first-line human immunodeficiency virus therapy with a CCR5 entry inhibitor, aplaviroc, plus a fixed-dose combination of lamivudine-zidovudine: nucleoside reverse transcriptase inhibitor resistance regardless of envelope tropism.Antimicrobial agents and chemotherapy · 2009Trial
- Murine norovirus mutants adapted to replicate in human cells reveal a post-entry restriction.Journal of virology · 2024Article
- The Phenomenon of Antiretroviral Drug Resistance in the Context of Human Immunodeficiency Virus Treatment: Dynamic and Ever Evolving Subject Matter.Biomedicines · 2024Review
- Murine norovirus mutants adapted to replicate in human cells reveal a post-entry restriction.bioRxiv : the preprint server for biology · 2024Article
- HIV and Drug-Resistant Subtypes.Microorganisms · 2023Review
- A Review: The Antiviral Activity of Cyclic Peptides.International journal of peptide research and therapeutics · 2023Review
- Enhancement of CD4 Binding, Host Cell Entry, and Sensitivity to CD4bs Antibody Inhibition Conferred by a Natural but Rare Polymorphism in the HIV-1 Envelope.Journal of virology · 2022Article
- V1 and V2 Domains of HIV Envelope Contribute to CCR5 Antagonist Resistance.Journal of virology · 2019Article
- Activity and structural analysis of GRL-117C: a novel small molecule CCR5 inhibitor active against R5-tropic HIV-1s.Scientific reports · 2019Article
- Concomitant Enhancement of HIV-1 Replication Potential and Neutralization-Resistance in Concert With Three Adaptive Mutations in Env V1/C2/C4 Domains.Frontiers in microbiology · 2019Article
- Opportunities for therapeutic antibodies directed at G-protein-coupled receptors.Nature reviews. Drug discovery · 2017Review
- CCR5 receptor antagonists in preclinical to phase II clinical development for treatment of HIV.Expert opinion on investigational drugs · 2016Review
- Reduced Baseline Sensitivity to Maraviroc Inhibition Among R5 HIV-1 Isolates From Individuals With Severe Immunodeficiency.Journal of acquired immune deficiency syndromes (1999) · 2016Article
- Incompatible Natures of the HIV-1 Envelope in Resistance to the CCR5 Antagonist Cenicriviroc and to Neutralizing Antibodies.Antimicrobial agents and chemotherapy · 2016Article
- Maraviroc: a review of its use in HIV infection and beyond.Drug design, development and therapy · 2015Review
- CCR5/CD4/CXCR4 oligomerization prevents HIV-1 gp120IIIB binding to the cell surface.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- V3-independent competitive resistance of a dual-X4 HIV-1 to the CXCR4 inhibitor AMD3100.PloS one · 2014Article
- Template-constrained cyclic sulfopeptide HIV-1 entry inhibitors.Organic & biomolecular chemistry · 2013Article
61 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
Abstract
To study HIV-1 escape from a coreceptor antagonist, the R5 primary isolate CC1/85 was passaged in peripheral blood mononuclear cells with increasing concentrations of the CCR5-specific small molecule inhibitor, AD101. By 19 passages, an escape mutant emerged with a >20,000-fold resistance to AD101. This virus was cross-resistant to a related inhibitor, SCH-C, and partially resistant to RANTES but still sensitive to CCR5-specific mAbs. The resistant phenotype was stable; the mutant virus retained AD101 resistance during nine additional passages of culture in the absence of inhibitor. Replication of the escape mutant in peripheral blood mononuclear cells completely depended on CCR5 expression and did not occur in cells from CCR5-Delta32 homozygous individuals. The escape mutant was unable to use CXCR4 or any other tested coreceptor to enter transfected cells. Acquisition of CXCR4 use is not the dominant in vitro escape pathway for a small molecule CCR5 entry inhibitor. Instead, HIV-1 acquires the ability to use CCR5 despite the inhibitor, first by requiring lower levels of CCR5 for entry and then probably by using the drug-bound form of the receptor.
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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.