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

被引：92

作者：

Tsibris, Athe M. N. ^{[1
,2
]}

Sagar, Manish ^{[2
,3
]}

Gulick, Roy M. ^{[4
]}

Su, Zhaohui ^{[5
]}

Hughes, Michael ^{[5
]}

Greaves, Wayne ^{[6
]}

Subramanian, Mani

Flexner, Charles ^{[7
]}

Giguel, Francoise ^{[1
]}

Leopold, Kay E. ^{[8
]}

Coakley, Eoin ^{[9
]}

Kuritzkes, Daniel R. ^{[2
,3
]}

机构：

[1] Massachusetts Gen Hosp, Boston, MA 02114 USA

[2] Harvard Univ, Sch Med, Boston, MA USA

[3] Brigham & Womens Hosp, Boston, MA 02115 USA

[4] Cornell Univ, Weill Med Coll, New York, NY 10021 USA

[5] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA

[6] Schering Plough Res Inst, Kenilworth, NJ USA

[7] Johns Hopkins Univ, Baltimore, MD USA

[8] Harvard Univ, Cambridge, MA 02138 USA

[9] Monogram Biosci, San Francisco, CA USA

来源：

JOURNAL OF VIROLOGY | 2008年 / 82卷 / 16期

关键词：

D O I：

10.1128/JVI.00444-08

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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 IIb 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.

引用

页码：8210 / 8214

页数：5

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