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

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.

• Authors: Tim Kümmerle, Clara Lehmann, Pia Hartmann, Christoph Wyen, Gerd Fätkenheuer
• Journal: Expert opinion on investigational drugs (Expert Opin Investig Drugs) Vol. 18 Issue 11 Pg. 1773-85 (Nov 2009) ISSN: 1744-7658 [Electronic] England
• PMID: 19888873 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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