Vicriviroc: a CCR5 antagonist for treatment-experienced patients with HIV-1 infection

Expert Opin Investig Drugs. 2009 Nov;18(11):1773-85. doi: 10.1517/13543780903357478.

Abstract

Background: Despite the availability of 31 antiretroviral agents or fixed-dose combinations in the United States and European Union, there is a continuing need for antiretroviral agents with high genetic barriers to resistance, simple dosing schedules, and favorable tolerability and safety profiles. Vicriviroc is a small-molecule chemokine receptor antagonist that inhibits the binding of R5-tropic HIV-1 to host cells at the CCR5 co-receptor, thus preventing viral entry.

Objective: To present an evidence-based assessment of the clinical efficacy, pharmacokinetics, and safety profile of vicriviroc.

Method: We discuss available peer-reviewed publications as well as preliminary data presented at relevant scientific meetings.

Results/conclusions: Vicriviroc has a favorable pharmacokinetic profile with a half-life that enables once-daily dosing. Minimal drug interactions have been demonstrated with other available antiretrovirals. Early clinical trials have established the safety of vicriviroc in both treatment-naive and treatment-experienced R5-tropic HIV-1 infected individuals. A Phase II study in treatment-experienced patients demonstrated early efficacy of 30 mg vicriviroc in a regimen containing a ritonavir-boosted protease inhibitor (PI/r). Phase III studies using the 30-mg PI/r dosing paradigm in R5-tropic treatment-experienced patients have completed 48 weeks, but data are not yet available. These results will further elucidate the role of vicriviroc in the treatment of HIV-1 infected individuals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / pharmacology
  • Anti-HIV Agents / therapeutic use*
  • CCR5 Receptor Antagonists
  • Clinical Trials as Topic
  • Drug Resistance, Viral
  • HIV Infections / drug therapy*
  • HIV-1 / drug effects
  • Humans
  • Piperazines / adverse effects
  • Piperazines / pharmacology
  • Piperazines / therapeutic use*
  • Pyrimidines / adverse effects
  • Pyrimidines / pharmacology
  • Pyrimidines / therapeutic use*
  • Virus Internalization / drug effects

Substances

  • Anti-HIV Agents
  • CCR5 Receptor Antagonists
  • Piperazines
  • Pyrimidines
  • vicriviroc