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
收藏
页码：8210 / 8214
页数：5
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