Maraviroc: A Coreceptor CCR5 Antagonist for Management of HIV Infection

Raymond Yost; Timothy R. Pasquale; Eric G. Sahloff


Am J Health Syst Pharm. 2009;66(8):715-726. 

In This Article

Abstract and Introduction


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.


Highly active antiretroviral therapy (HAART) has revolutionized the treatment of human immunodeficiency virus (HIV) infection over the past 10 years. Patients and clinicians have more choices in antiretroviral agents now than in the early 1990s or even at the beginning of this decade. New agents for previously identified drug targets, such as reverse transcriptase and protease, have been approved for marketing, along with a new fusion inhibitor and integrase inhibitor. Despite these advances in the treatment of HIV, the complete eradication of infection with the virus is still not possible. Increasing resistance, nonadherence to medications, and toxicity have fueled virological failure and the need for additional agents active against HIV. The concept of HIV-entry inhibition was introduced into practice in 2003 with the approval of enfuvirtide, the first HIV fusion inhibitor.[1] Coreceptor CCR5 antagonists, which provide a novel mechanism of action, are a recent addition to the armamentarium of antiretroviral agents.

Maraviroc (Selzentry, Pfizer Inc., New York, NY) was approved for marketing by the Food and Drug Administration (FDA) on August 6, 2007, for use in combination with other antiretroviral agents in the treatment of HAART-experienced adult patients whose HIV infection is resistant to multiple classes of anti-retroviral drugs. In addition, maraviroc is labeled for use only in patients infected with CCR5-tropic HIV-1, who have evidence of ongoing viral replication, and who are resistant to multiple antiretroviral agents.[2] Maraviroc is the first approved CCR5 antagonist and has a novel mechanism of action.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: