Three-year safety and efficacy of vicriviroc, a CCR5 antagonist, in hiv-1-infected treatment-experienced patients

Timothy J. Wilkin, Zhaohui Su, Amy Krambrink, Jianmin Long, Wayne Greaves, Robert Gross, Michael D. Hughes, Charles Flexner, Paul R. Skolnik, Eoin Coakley, Catherine Godfrey, Martin Hirsch, Daniel R. Kuritzkes, Roy M. Gulick

Research output: Contribution to journalArticle

Abstract

Background: Vicriviroc, an investigational CCR5 antagonist, demonstrated short-term safety and antiretroviral activity. Methods: Phase 2, double-blind, randomized study of vicriviroc in treatment-experienced subjects with CCR5-using HIV-1. Vicriviroc (5, 10, or 15 mg) or placebo was added to a failing regimen with optimization of background antiretroviral medications at day 14. Subjects experiencing virologic failure and subjects completing 48 weeks were offered open-label vicriviroc. Results: One hundred eighteen subjects were randomized. Virologic failure (<1 log10 decline in HIV-1 RNA ≥16 weeks postrandomization) occurred by week 48 in 24 of 28 (86%), 12 of 30 (40%), 8 of 30 (27%), 10 of 30 (33%) of subjects randomized to placebo, 5, 10, and 15 mg, respectively. Overall, 113 subjects received vicriviroc at randomization or after virologic failure, and 52 (46%) achieved HIV-1 RNA <50 copies per milliliter within 24 weeks. Through 3 years, 49% of those achieving suppression did not experience confirmed viral rebound. Dual or mixed-tropic HIV-1 was detected in 33 (29%). Vicriviroc resistance (progressive decrease in maximal percentage inhibition on phenotypic testing) was detected in 6 subjects. Nine subjects discontinued vicriviroc due to adverse events. Conclusions: Vicriviroc seems safe and demonstrates sustained virologic suppression through 3 years of follow-up. Further trials of vicriviroc will establish its clinical utility for the treatment of HIV-1 infection.

Original languageEnglish (US)
Pages (from-to)470-476
Number of pages7
JournalJournal of acquired immune deficiency syndromes
Volume54
Issue number5
DOIs
StatePublished - Aug 15 2010

Keywords

  • CCR5 antagonist
  • HIV-1
  • antiretroviral therapy

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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    Wilkin, T. J., Su, Z., Krambrink, A., Long, J., Greaves, W., Gross, R., Hughes, M. D., Flexner, C., Skolnik, P. R., Coakley, E., Godfrey, C., Hirsch, M., Kuritzkes, D. R., & Gulick, R. M. (2010). Three-year safety and efficacy of vicriviroc, a CCR5 antagonist, in hiv-1-infected treatment-experienced patients. Journal of acquired immune deficiency syndromes, 54(5), 470-476. https://doi.org/10.1097/QAI.0b013e3181e2cba0