ArticleAIDS research and human retroviruses2010
HIV type 1 from a patient with baseline resistance to CCR5 antagonists uses drug-bound receptor for entry.
Article in AIDS research and human retroviruses, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 55 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
- New Therapies and Strategies to Curb HIV Infections with a Focus on Macrophages and Reservoirs.Viruses · 2024Review
- Article
- 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
- Full Length Single Chain Fc Protein (FLSC IgG1) as a Potent Antiviral Therapy Candidate: Implications for In Vivo Studies.AIDS research and human retroviruses · 2016Article
- Characterizing the Diverse Mutational Pathways Associated with R5-Tropic Maraviroc Resistance: HIV-1 That Uses the Drug-Bound CCR5 Coreceptor.Journal of virology · 2015Article
- C-C chemokine receptor type five (CCR5): An emerging target for the control of HIV infection.Applied & translational genomics · 2013Review
- Template-constrained cyclic sulfopeptide HIV-1 entry inhibitors.Organic & biomolecular chemistry · 2013Article
- Activity of the HIV-1 attachment inhibitor BMS-626529, the active component of the prodrug BMS-663068, against CD4-independent viruses and HIV-1 envelopes resistant to other entry inhibitors.Antimicrobial agents and chemotherapy · 2013Article
- Comparison of viral Env proteins from acute and chronic infections with subtype C human immunodeficiency virus type 1 identifies differences in glycosylation and CCR5 utilization and suggests a new strategy for immunogen design.Journal of virology · 2013Article
- Use of G-protein-coupled and -uncoupled CCR5 receptors by CCR5 inhibitor-resistant and -sensitive human immunodeficiency virus type 1 variants.Journal of virology · 2013Article
- A common mechanism of clinical HIV-1 resistance to the CCR5 antagonist maraviroc despite divergent resistance levels and lack of common gp120 resistance mutations.Retrovirology · 2013Article
- Constitutively active CCR5 chemokine receptors differ in mediating HIV envelope-dependent fusion.PloS one · 2013Article
- Structure and dynamics of the gp120 V3 loop that confers noncompetitive resistance in R5 HIV-1(JR-FL) to maraviroc.PloS one · 2013Article
- Review
- Article
- Differential use of CCR5 by HIV-1 clinical isolates resistant to small-molecule CCR5 antagonists.Antimicrobial agents and chemotherapy · 2012Article
- Transmitted/founder and chronic subtype C HIV-1 use CD4 and CCR5 receptors with equal efficiency and are not inhibited by blocking the integrin α4β7.PLoS pathogens · 2012Article
- Stochastic model of in-vivo X4 emergence during HIV infection: implications for the CCR5 inhibitor maraviroc.PloS one · 2012Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
CCR5 antagonists are a new class of antiretroviral drugs that block viral entry by disrupting interactions between the viral envelope (Env) glycoprotein and coreceptor. During the CCR100136 (EPIC) Phase IIb study of the CCR5 antagonist aplaviroc (APL) in treatment-naive individuals, a patient was identified who harbored virus strains that exhibited partial resistance to APL at the time of virologic failure. Retrospectively, it was found that APL resistance was present at baseline as well. To investigate the mechanism of APL resistance in this patient, we cloned HIV-1 env genes from plasma obtained at baseline and after virologic failure. Approximately 85% of cloned Envs were functional, and all exhibited partial resistance to APL. All Envs were R5-tropic, were partially resistant to other CCR5 antagonists including maraviroc on cells with high CCR5 expression, but remained sensitive to the fusion inhibitor enfuvirtide. Competition studies with natural CCR5 ligands revealed that the mechanism of drug resistance entailed the use of the drug-bound conformation of CCR5 by the Env proteins obtained from this individual. The degree of drug resistance varied between Env clones, and also varied depending on the cell line used or the donor from whom the primary T cells were obtained. Thus, both virus and host factors contribute to CCR5 antagonist resistance. This study shows that R5 HIV-1 strains resistant to CCR5 inhibitors can arise in patients, confirming a mechanism of resistance previously characterized in vitro. In addition, some patients can harbor CCR5 antagonist-resistant viruses prior to treatment, which may have implications for the clinical use of this new class of antiretrovirals.
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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.