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

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Tsibris AM, Sagar M, Gulick RM, Su Z, Hughes M, Greaves W, Subramanian M, Flexner C, Giguel F, Leopold KE, Coakley E, Kuritzkes DR

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

J Virol. 2008 Aug;82(16):8210-4. doi: 10.1128/JVI.00444-08. Epub 2008 May 21.

PubMed ID

18495779 [ View in PubMed

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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 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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Vicriviroc	C-C chemokine receptor type 5	Protein	Humans	Unknown	Antagonist	Details