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Development of maraviroc, a CCR5 antagonist for treatment of HIV, using a novel tropism assay.
- Source :
-
Annals of the New York Academy of Sciences [Ann N Y Acad Sci] 2015 Jun; Vol. 1346 (1), pp. 7-17. Date of Electronic Publication: 2015 May 11. - Publication Year :
- 2015
-
Abstract
- Assays to identify infectious organisms are critical for diagnosis and enabling the development of therapeutic agents. The demonstration that individuals with a 32-bp deletion within the CCR5 locus were resistant to human immunodeficiency virus (HIV) infection, while those heterozygous for the mutation progressed more slowly, led to the discovery of maraviroc (MVC), a CCR5 antagonist. As MVC is only active against CCR5-tropic strains of HIV, it was critical to develop a diagnostic assay to identify appropriate patients. Trofileā¢, a novel phenotypic tropism assay, was used to identify patients with CCR5-tropic virus for the MVC development program. Results of these clinical studies demonstrated that the assay correctly identified patients likely to respond to MVC. Over time, the performance characteristics of the phenotypic assay were enhanced, necessitating retesting of study samples. Genotypic tropism tests that have the potential to allow for local use and more rapid turnaround times are also being developed.<br /> (© 2015 New York Academy of Sciences.)
- Subjects :
- Biological Assay methods
Clinical Trials as Topic
Drug Design
Drug Evaluation, Preclinical methods
HIV-1 drug effects
Humans
Maraviroc
Receptors, CCR5 drug effects
Receptors, CCR5 metabolism
Anti-HIV Agents chemical synthesis
Anti-HIV Agents chemistry
Anti-HIV Agents therapeutic use
Cyclohexanes chemical synthesis
Cyclohexanes chemistry
Cyclohexanes pharmacology
HIV Infections drug therapy
HIV-1 physiology
Triazoles chemical synthesis
Triazoles chemistry
Triazoles pharmacology
Viral Tropism drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1749-6632
- Volume :
- 1346
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Annals of the New York Academy of Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 25962411
- Full Text :
- https://doi.org/10.1111/nyas.12777