Background:

Maraviroc is unique among approved antiretroviral drugs in targeting the host-cell chemokine coreceptor type-5 receptor. With its novel mechanism of action, we sought to describe the 5-year safety profile of maraviroc.

Methods:

Two large phase 3 studies of maraviroc enrolled HIV-infected treatment-experienced patients and followed them up for 5 or more years. Survival and selected clinical end points were identified and assessed.

Results:

A total of 938 enrolled patients received maraviroc-containing regimens. Rates of death and selected clinical events (eg, hepatic failure, malignancy, and myocardial infarction) were low during follow-up.

Conclusions:

Maraviroc was generally safe in treatment-experienced participants for> 5 years.

INTRODUCTION

Maraviroc is a first-in-class selective chemokine coreceptor type-5 (CCR5) antagonist that demonstrated antiretroviral activity in early phase 2a studies of HIV-infected patients with CCR5-tropic (R5) virus. 1 Maraviroc has a unique mechanism of action among approved antiretrovirals in binding to a host protein, the CCR5 receptor, rather than a viral target. Maraviroc binds to the CCR5 receptor and prevents the interaction of the external membrane glycoprotein of R5 HIV-1, gp120, with the host cell receptor. Given the unique mode of action and use of a host-cell target, initial concerns existed about the potential safety of CCR5 antagonists, including maraviroc. 2 Also, early development of other investigational CCR5 antagonists demonstrated potential class-specific effects: aplaviroc was associated with severe hepatotoxicity, 3 and further clinical development was stopped; vicriviroc was initially associated with malignancies in a phase 2 study, 4 although this was not confirmed in larger phase 3 studies. 5