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

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Pages (from-to)8210-8214
Number of pages5
JournalJournal of virology
Volume82
Issue number16
DOIs
StatePublished - Aug 2008

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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