Journal article
A common mechanism of clinical HIV-1 resistance to the CCR5 antagonist maraviroc despite divergent resistance levels and lack of common gp120 resistance mutations
M Roche, H Salimi, R Duncan, BL Wilkinson, K Chikere, MS Moore, NE Webb, H Zappi, J Sterjovski, JK Flynn, A Ellett, LR Gray, B Lee, B Jubb, M Westby, PA Ramsland, SR Lewin, RJ Payne, MJ Churchill, PR Gorry
Retrovirology | Published : 2013
Abstract
Background: The CCR5 antagonist maraviroc (MVC) inhibits human immunodeficiency virus type 1 (HIV-1) entry by altering the CCR5 extracellular loops (ECL), such that the gp120 envelope glycoproteins (Env) no longer recognize CCR5. The mechanisms of HIV-1 resistance to MVC, the only CCR5 antagonist licensed for clinical use are poorly understood, with insights into MVC resistance almost exclusively limited to knowledge obtained from in vitro studies or from studies of resistance to other CCR5 antagonists. To more precisely understand mechanisms of resistance to MVC in vivo, we characterized Envs isolated from 2 subjects who experienced virologic failure on MVC.Results: Envs were cloned from su..
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Awarded by National Institute of Allergy and Infectious Diseases
Funding Acknowledgements
This study was supported by a grant from the Australian National Health and Medical Research Council to PRG, MJC and SRL (1006534). PRG was the recipient of an Australian National Health and Medical Research Council (NHMRC) Level 2 Biomedical Career Development Award, and is now supported by an Australian Research Council (ARC) Future Fellowship (FT2). HS is supported by a Postgraduate Research Scholarship from the Iranian Ministry of Health and Medical Education. LRG is the recipient of an Australian NHMRC Postdoctoral Training Fellowship. SRL is the recipient of a NHMRC Practitioner Fellowship. The authors gratefully acknowledge the contribution to this work of the Victorian Operational Infrastructure Support Program received by the Burnet Institute.