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

J Acquir Immune Defic Syndr. 2010 Aug;54(5):470-6. doi: 10.1097/qai.0b013e3181e2cba0.

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 > or =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.

Trial registration: ClinicalTrials.gov NCT00082498.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / adverse effects*
  • Female
  • HIV Infections / drug therapy*
  • HIV-1 / drug effects*
  • Humans
  • Male
  • Middle Aged
  • Piperazines / administration & dosage*
  • Piperazines / adverse effects*
  • Placebos / administration & dosage
  • Pyrimidines / administration & dosage*
  • Pyrimidines / adverse effects*
  • Treatment Outcome
  • Viral Load

Substances

  • Anti-HIV Agents
  • Piperazines
  • Placebos
  • Pyrimidines
  • vicriviroc

Associated data

  • ClinicalTrials.gov/NCT00082498

Grant support