Maraviroc: A CCR5-receptor antagonist for the treatment of HIV-1 infection

• Published in: Clinical therapeutics 2008-07, Vol.30 (7), p.1228-1250
• Main Authors: Lieberman-Blum, Sharon S., PharmD, Fung, Horatio B., PharmD, BCPS, Bandres, Juan C., MD, PhD
• Format: Article
• Language: English
• Subjects: Anti-HIV Agents - economics; Anti-HIV Agents - pharmacokinetics; Anti-HIV Agents - pharmacology; Anti-HIV Agents - therapeutic use; Biological and medical sciences; CCR5 Receptor Antagonists; CCR5-receptor antagonist; Chemokines; Cyclohexanes - economics; Cyclohexanes - pharmacokinetics; Cyclohexanes - pharmacology; Cyclohexanes - therapeutic use; Drug Interactions; Drug resistance; Drug Resistance, Multiple, Viral; entry inhibitor; HIV; HIV Infections - drug therapy; HIV-1 - drug effects; HIV-1 infection; Human immunodeficiency virus; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infections; Infectious diseases; Internal Medicine; maraviroc; Medical Education; Medical sciences; Patients; Pharmacokinetics; Pharmacology. Drug treatments; Triazoles - economics; Triazoles - pharmacokinetics; Triazoles - pharmacology; Triazoles - therapeutic use; Veterans; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/S0149-2918(08)80048-3

Abstract Background: The emergence of viral resistance is one of the greatest challenges in the treatment of HIV infection. Maraviroc is the first member of a new class of antiretroviral medications, the CCR5-receptor antagonists. It is approved by the US Food and Drug Administration (FDA) for use in combination with other antiretroviral agents in treatment-experienced patients infected with multidrug-resistant, CCR5-tropic HIV-1. Objective: This article provides an overview of the pharmacology, efficacy, and tolerability of maraviroc in the treatment of HIV-1 infection. Methods: Relevant information was identified through a search of MEDLINE (January 2000-May 2008) using the terms maraviroc , UK-427,857 , and CCR5-receptor antagonist . Also consulted were abstracts from the International AIDS Society Conference, the Conference on Retroviruses and Opportunistic Infections, and other relevant scientific meetings. Additional publications were found by searching the reference lists of the identified articles and the FDA Web site. Results: Maraviroc is a selective, reversible, small-molecule CCR5-receptor antagonist. In vitro, it has potent anti-HIV-1 activity, with a mean 90% inhibitory concentration of 2.0 nmol/L. It is widely distributed, with a Vd of ~194 L. Maraviroc is moderately metabolized in the liver (65.3%), primarily via the cytochrome P450 3A4 isozyme. It has an elimination t1/2 of 15.9 to 22.9 hours. Until more data are available, maraviroc should be avoided in patients with severe hepatic insufficiency; dose adjustment does not appear to be necessary on the basis of age, sex, or renal function. In 2 Phase IIb/III studies, maraviroc 300 mg PO QD or BID was found to be more efficacious than placebo in reducing the viral load at 48 weeks in treatment-experienced, CCR5-tropic HIV-1-infected patients receiving an optimized background regimen (difference vs placebo—QD arm: -0.89 log10 copies/mL [97.5% CI, -1.17 to -0.62]; BID arm: -1.05 log10 copies/mL [97.5% CI, -1.33 to -0.78]). The proportion of patients with a viral load