ArticleJournal of acquired immune deficiency syndromes (1999)2010
Evolution of CCR5 antagonist resistance in an HIV-1 subtype C clinical isolate.
Article in Journal of acquired immune deficiency syndromes (1999), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Evolution of Multiple Domains of the HIV-1 Envelope Glycoprotein during Coreceptor Switch with CCR5 Antagonist Therapy.Microbiology spectrum · 2022Trial
- Vicriviroc resistance decay and relative replicative fitness in HIV-1 clinical isolates under sequential drug selection pressures.Journal of virology · 2012Trial
- HIV-1 clinical isolates resistant to CCR5 antagonists exhibit delayed entry kinetics that are corrected in the presence of drug.Journal of virology · 2012Trial
- V1 and V2 Domains of HIV Envelope Contribute to CCR5 Antagonist Resistance.Journal of virology · 2019Article
- Frequency and Env determinants of HIV-1 subtype C strains from antiretroviral therapy-naive subjects that display incomplete inhibition by maraviroc.Retrovirology · 2016Article
- Incompatible Natures of the HIV-1 Envelope in Resistance to the CCR5 Antagonist Cenicriviroc and to Neutralizing Antibodies.Antimicrobial agents and chemotherapy · 2016Article
- Viremic control and viral coreceptor usage in two HIV-1-infected persons homozygous for CCR5 Δ32.AIDS (London, England) · 2015Article
- Genome-Wide Association Study of Human Immunodeficiency Virus (HIV)-1 Coreceptor Usage in Treatment-Naive Patients from An AIDS Clinical Trials Group Study.Open forum infectious diseases · 2014Article
- Nanostructured optical photonic crystal biosensor for HIV viral load measurement.Scientific reports · 2014Article
- Long-term reduction in peripheral blood HIV type 1 reservoirs following reduced-intensity conditioning allogeneic stem cell transplantation.The Journal of infectious diseases · 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
- Sensitivity changes over the course of infection increases the likelihood of resistance against fusion but not CCR5 receptor blockers.AIDS research and human retroviruses · 2012Article
- Review
- Differential use of CCR5 by HIV-1 clinical isolates resistant to small-molecule CCR5 antagonists.Antimicrobial agents and chemotherapy · 2012Article
- Drug resistance in HIV-1.Current opinion in virology · 2011Review
- SHIV-162P3 infection of rhesus macaques given maraviroc gel vaginally does not involve resistant viruses.PloS one · 2011Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
objectivesWe previously reported vicriviroc (VCV) resistance in an HIV-infected subject and used deep sequencing and clonal analyses to track the evolution of V3 sequence forms over 28 weeks of therapy. Here, we test the contribution of gp120 mutations to CCR5 antagonist resistance and investigate why certain minority V3 variants emerged as the dominant species under drug pressure.
methodsNineteen site-directed HIV-1 mutants were generated that contained gp120 VCV resistance mutations. Viral sensitivities to VCV, maraviroc, TAK-779, and HGS004 were determined.
resultsThree patterns of susceptibilities were observed as follows: sigmoid inhibition curves with 50% inhibitory concentration similar to pretreatment virus [07J-week 0 (W0)], single mutants with decreased 50% inhibitory concentrations compared with 07J-W0, and mutants that contained ≥5 of 7 VCV resistance mutations with flattened inhibition curves and decreased or negative percent maximal inhibition. Substitutions such as S306P, which sensitized virus to CCR5 antagonists when present as single mutations, were not detected in the baseline virus population but were necessary for maximal resistance when incorporated into V3 backbones that included preexisting VCV resistance mutations.
conclusionsCCR5 antagonist resistance was reproduced only when a majority of V3 mutations were present. Minority V3 loop variants may serve as a scaffold upon which additional mutations lead to complete VCV resistance.
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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.