In vivo emergence of vicriviroc resistance in a human immunodeficiency virus type 1 subtype C-infected subject

Athe M.N. Tsibris; Manish Sagar; Roy M. Gulick; Zhaohui Su; Michael Hughes; Wayne Greaves; Mani Subramanian; Charles Flexner; Françoise Giguel; Kay E. Leopold; Eoin Coakley; Daniel R. Kuritzkes

doi:10.1128/JVI.00444-08

In vivo emergence of vicriviroc resistance in a human immunodeficiency virus type 1 subtype C-infected subject

Athe M.N. Tsibris, Manish Sagar, Roy M. Gulick, Zhaohui Su, Michael Hughes, Wayne Greaves, Mani Subramanian, Charles Flexner, Françoise Giguel, Kay E. Leopold, Eoin Coakley, Daniel R. Kuritzkes

School of Medicine

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

99 Scopus citations

Abstract

Little is known about the in vivo development of resistance to human immunodeficiency virus type 1 (HIV-1) CCR5 antagonists. We studied 29 subjects with virologic failure from a phase lib study of the CCR5 antagonist vicriviroc (VCV) and identified one individual with HIV-1 subtype C who developed VCV resistance. Studies with chimeric envelopes demonstrated that changes within the V3 loop were sufficient to confer VCV resistance. Resistant virus showed VCV-enhanced replication, cross-resistance to another CCR5 antagonist, TAK779, and increased sensitivity to aminooxypentane-RANTES and the CCR5 monoclonal antibody HGS004. Pretreatment V3 loop sequences reemerged following VCV discontinuation, implying that VCV resistance has associated fitness costs.

Original language	English (US)
Pages (from-to)	8210-8214
Number of pages	5
Journal	Journal of virology
Volume	82
Issue number	16
DOIs	https://doi.org/10.1128/JVI.00444-08
State	Published - Aug 2008

ASJC Scopus subject areas

Microbiology
Immunology
Insect Science
Virology

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title = "In vivo emergence of vicriviroc resistance in a human immunodeficiency virus type 1 subtype C-infected subject",

abstract = "Little is known about the in vivo development of resistance to human immunodeficiency virus type 1 (HIV-1) CCR5 antagonists. We studied 29 subjects with virologic failure from a phase lib study of the CCR5 antagonist vicriviroc (VCV) and identified one individual with HIV-1 subtype C who developed VCV resistance. Studies with chimeric envelopes demonstrated that changes within the V3 loop were sufficient to confer VCV resistance. Resistant virus showed VCV-enhanced replication, cross-resistance to another CCR5 antagonist, TAK779, and increased sensitivity to aminooxypentane-RANTES and the CCR5 monoclonal antibody HGS004. Pretreatment V3 loop sequences reemerged following VCV discontinuation, implying that VCV resistance has associated fitness costs.",

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AU - Tsibris, Athe M.N.

AU - Sagar, Manish

AU - Gulick, Roy M.

AU - Su, Zhaohui

AU - Hughes, Michael

AU - Greaves, Wayne

AU - Subramanian, Mani

AU - Flexner, Charles

AU - Giguel, Françoise

AU - Leopold, Kay E.

AU - Coakley, Eoin

AU - Kuritzkes, Daniel R.

PY - 2008/8

Y1 - 2008/8

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AB - Little is known about the in vivo development of resistance to human immunodeficiency virus type 1 (HIV-1) CCR5 antagonists. We studied 29 subjects with virologic failure from a phase lib study of the CCR5 antagonist vicriviroc (VCV) and identified one individual with HIV-1 subtype C who developed VCV resistance. Studies with chimeric envelopes demonstrated that changes within the V3 loop were sufficient to confer VCV resistance. Resistant virus showed VCV-enhanced replication, cross-resistance to another CCR5 antagonist, TAK779, and increased sensitivity to aminooxypentane-RANTES and the CCR5 monoclonal antibody HGS004. Pretreatment V3 loop sequences reemerged following VCV discontinuation, implying that VCV resistance has associated fitness costs.

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In vivo emergence of vicriviroc resistance in a human immunodeficiency virus type 1 subtype C-infected subject

Abstract

ASJC Scopus subject areas

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