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

TitleIn vivo emergence of vicriviroc resistance in a human immunodeficiency virus type 1 subtype C-infected subject.
Publication TypeJournal Article
Year of Publication2008
AuthorsTsibris AMN, Sagar M, Gulick RM, Su Z, Hughes M, Greaves W, Subramanian M, Flexner C, Giguel F, Leopold KE, Coakley E, Kuritzkes DR
JournalJ Virol
Volume82
Issue16
Pagination8210-4
Date Published2008 Aug
ISSN1098-5514
KeywordsAmino Acid Sequence, Anti-HIV Agents, Antibodies, Monoclonal, CCR5 Receptor Antagonists, DNA Primers, Drug Resistance, Viral, HIV Infections, HIV-1, Humans, Molecular Sequence Data, Piperazines, Pyrimidines, Receptors, CCR5, Recombination, Genetic, Sequence Homology, Amino Acid, Time Factors, Viral Envelope Proteins
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.

DOI10.1128/JVI.00444-08
Alternate JournalJ. Virol.
PubMed ID18495779
PubMed Central IDPMC2519584
Grant ListK24 AI-51966 / AI / NIAID NIH HHS / United States
K24 RR016482 / RR / NCRR NIH HHS / United States
P30 AI060354 / AI / NIAID NIH HHS / United States
R37 AI553537 / AI / NIAID NIH HHS / United States
T32 AI007387 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States