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American Journal of Health-System Pharmacy, Vol. 66, Issue 8, 715-726
Copyright © 2009. American Society of Health-System Pharmacists, Inc. All rights reserved. 1079-2082/04/0602-1242$06.00


Clinical Review

Maraviroc: A coreceptor CCR5 antagonist for management of HIV infection

Raymond Yost, Timothy R. Pasquale and Eric G. Sahloff

RAYMOND YOST, PHARM.D., is Pharmacy Practice Resident; and TIMOTHY R. PASQUALE, PHARM.D., is Clinical Lead—Infectious Diseases, Summa Health System, Akron, OH. ERIC G. SAHLOFF, PHARM D., is Assistant Professor of Pharmacy Practice, College of Pharmacy, University of Toledo, Toledo, OH.

Address correspondence to Dr. Sahloff at the College of Pharmacy, University of Toledo, 2801 West Bancroft, MS 609, Toledo, OH 43606, (eric.sahloff{at}utoledo.edu).


Purpose. The mechanism of action, pharmacology, pharmacokinetics, clinical efficacy, drug interactions, adverse effects, dosage and administration, cost, and role in therapy of maraviroc are reviewed.

Summary. Maraviroc is the first CCR5 coreceptor antagonist to receive marketing approval from the Food and Drug Administration (FDA) for the treatment of CCR5-tropic human immunodeficiency virus (HIV) infection as part of an optimized antiretroviral regimen in treatment-experienced patients. As 50% or more of treatment-experienced patients may be infected with CXCR4-tropic virus, a tropism assay should be performed before initiating maraviroc therapy. The majority of evidence supporting maraviroc’s use comes from two studies of HIV-infected, treatment-experienced patients. Pooled analysis from these two studies revealed that twice-daily maraviroc decreased HIV-1 RNA by 1.84 log copies/mL, compared with 0.78 log copy/mL with placebo. Forty-six percent of subjects attained an HIV-1 RNA concentration of <50 copies/mL, compared with only 17% with placebo. In a trial of treatment-naive HIV-infected individuals, maraviroc failed to show noninferiority to efavirenz. Maraviroc is metabolized by cytochrome P-450 isoenzyme 3A4 and is subject to interactions with inhibitors and inducers of that isoenzyme, such as the protease inhibitors (except tipranavir), efavirenz, and rifampin. Resistance has been reported with maraviroc, but specific mechanisms are still poorly understood. The most common adverse effects reported with maraviroc were diarrhea, nausea, fatigue, and headache.

Conclusion. Available data support the use of maraviroc, the first CCR5 antagonist to receive FDA marketing approval, as part of an optimized antiretroviral regimen in treatment-experienced patients infected with CCR5-tropic HIV.

Index terms: Antiretroviral agents; Costs; Dosage; Drug administration; Drug interactions; HIV infections; Maraviroc; Mechanism of action; Metabolism; Pharmacokinetics; Resistance; Toxicity

 



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