A common mechanism of clinical HIV-1 resistance to the CCR5 antagonist maraviroc despite divergent resistance levels and lack of common gp120 resistance mutations

Michael John Roche; Hamid Salimi; Renee Charlene Duncan; Brendan Wilkinson; Kelechi Chikere; Miranda S Moore; Nicholas Webb; Helena Zappi; Jasminka Sterjovski; Jacqueline Kaye Flynn; Anne Ellett; Lachlan Robert Gray; Benhur Lee; Becky Jubb; Mike Westby; Paul Allen Ramsland; Sharon Ruth Lewin; Richard J Payne; Melissa Churchill; Paul R Gorry

doi:10.1186/1742-4690-10-43

A common mechanism of clinical HIV-1 resistance to the CCR5 antagonist maraviroc despite divergent resistance levels and lack of common gp120 resistance mutations

Michael John Roche, Hamid Salimi, Renee Charlene Duncan, Brendan Wilkinson, Kelechi Chikere, Miranda S Moore, Nicholas Webb, Helena Zappi, Jasminka Sterjovski, Jacqueline Kaye Flynn, Anne Ellett, Lachlan Robert Gray, Benhur Lee, Becky Jubb, Mike Westby, Paul Allen Ramsland, Sharon Ruth Lewin, Richard J Payne, Melissa Churchill, Paul R Gorry

Research output: Contribution to journal › Article › Research › peer-review

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Abstract

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.

Original language	English
Pages (from-to)	1 - 20
Number of pages	20
Journal	Retrovirology
Volume	10
Issue number	1 (Art. No.: 43)
DOIs	https://doi.org/10.1186/1742-4690-10-43
Publication status	Published - 2013

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Roche, M. J., Salimi, H., Duncan, R. C., Wilkinson, B., Chikere, K., Moore, M. S., Webb, N., Zappi, H., Sterjovski, J., Flynn, J. K., Ellett, A., Gray, L. R., Lee, B., Jubb, B., Westby, M., Ramsland, P. A., Lewin, S. R., Payne, R. J., Churchill, M., & Gorry, P. R. (2013). 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, 10(1 (Art. No.: 43)), 1 - 20. https://doi.org/10.1186/1742-4690-10-43

Roche, Michael John ; Salimi, Hamid ; Duncan, Renee Charlene ; Wilkinson, Brendan ; Chikere, Kelechi ; Moore, Miranda S ; Webb, Nicholas ; Zappi, Helena ; Sterjovski, Jasminka ; Flynn, Jacqueline Kaye ; Ellett, Anne ; Gray, Lachlan Robert ; Lee, Benhur ; Jubb, Becky ; Westby, Mike ; Ramsland, Paul Allen ; Lewin, Sharon Ruth ; Payne, Richard J ; Churchill, Melissa ; Gorry, Paul R. / A common mechanism of clinical HIV-1 resistance to the CCR5 antagonist maraviroc despite divergent resistance levels and lack of common gp120 resistance mutations. In: Retrovirology. 2013 ; Vol. 10, No. 1 (Art. No.: 43). pp. 1 - 20.

@article{40e1c2213ee843a1a24623b6ac42cac0,

title = "A common mechanism of clinical HIV-1 resistance to the CCR5 antagonist maraviroc despite divergent resistance levels and lack of common gp120 resistance mutations",

abstract = "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.",

author = "Roche, {Michael John} and Hamid Salimi and Duncan, {Renee Charlene} and Brendan Wilkinson and Kelechi Chikere and Moore, {Miranda S} and Nicholas Webb and Helena Zappi and Jasminka Sterjovski and Flynn, {Jacqueline Kaye} and Anne Ellett and Gray, {Lachlan Robert} and Benhur Lee and Becky Jubb and Mike Westby and Ramsland, {Paul Allen} and Lewin, {Sharon Ruth} and Payne, {Richard J} and Melissa Churchill and Gorry, {Paul R}",

year = "2013",

doi = "10.1186/1742-4690-10-43",

language = "English",

volume = "10",

pages = "1 -- 20",

journal = "Retrovirology",

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number = "1 (Art. No.: 43)",

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Roche, MJ, Salimi, H, Duncan, RC, Wilkinson, B, Chikere, K, Moore, MS, Webb, N, Zappi, H, Sterjovski, J, Flynn, JK, Ellett, A, Gray, LR, Lee, B, Jubb, B, Westby, M, Ramsland, PA , Lewin, SR, Payne, RJ, Churchill, M & Gorry, PR 2013, '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, vol. 10, no. 1 (Art. No.: 43), pp. 1 - 20. https://doi.org/10.1186/1742-4690-10-43

A common mechanism of clinical HIV-1 resistance to the CCR5 antagonist maraviroc despite divergent resistance levels and lack of common gp120 resistance mutations. / Roche, Michael John; Salimi, Hamid; Duncan, Renee Charlene; Wilkinson, Brendan; Chikere, Kelechi; Moore, Miranda S; Webb, Nicholas; Zappi, Helena; Sterjovski, Jasminka; Flynn, Jacqueline Kaye; Ellett, Anne; Gray, Lachlan Robert; Lee, Benhur; Jubb, Becky; Westby, Mike; Ramsland, Paul Allen ; Lewin, Sharon Ruth; Payne, Richard J; Churchill, Melissa; Gorry, Paul R.

In: Retrovirology, Vol. 10, No. 1 (Art. No.: 43), 2013, p. 1 - 20.

Research output: Contribution to journal › Article › Research › peer-review

TY - JOUR

T1 - A common mechanism of clinical HIV-1 resistance to the CCR5 antagonist maraviroc despite divergent resistance levels and lack of common gp120 resistance mutations

AU - Roche, Michael John

AU - Salimi, Hamid

AU - Duncan, Renee Charlene

AU - Wilkinson, Brendan

AU - Chikere, Kelechi

AU - Moore, Miranda S

AU - Webb, Nicholas

AU - Zappi, Helena

AU - Sterjovski, Jasminka

AU - Flynn, Jacqueline Kaye

AU - Ellett, Anne

AU - Gray, Lachlan Robert

AU - Lee, Benhur

AU - Jubb, Becky

AU - Westby, Mike

AU - Ramsland, Paul Allen

AU - Lewin, Sharon Ruth

AU - Payne, Richard J

AU - Churchill, Melissa

AU - Gorry, Paul R

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648390/pdf/1742-4690-10-43.pdf

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DO - 10.1186/1742-4690-10-43

M3 - Article

VL - 10

SP - 1

EP - 20

JO - Retrovirology

JF - Retrovirology

SN - 1742-4690

IS - 1 (Art. No.: 43)

ER -

A common mechanism of clinical HIV-1 resistance to the CCR5 antagonist maraviroc despite divergent resistance levels and lack of common gp120 resistance mutations

Abstract

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