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Maraviroc Induced CCR5 Blockage for HIV Infected Individuals is Associated with Increased Rates of Respiratory Tract Infections

Yoav Keynan, Ethan Rubinstein, Ken Kasper and Keith R. Fowke

Background: Maraviroc is an allosteric, non-competitive blocker of CCR5, interfering with its ability to bind to the HIV GP120 and thus preventing HIV cell entry. CCR5 is involved in recruiting immune cells to sites of viral invasion in the respiratory tract.

This postulated role of CCR5 led us to perform a meta-analysis of the largest clinical drug trials that evaluated CCR5 antagonists, as part of antiretroviral regimens, with focus on the occurrence of respiratory infections in general and viral infections in particular in CCR5 antagonist recipients.

Data source and eligibility criteria: Clinical trials involving administration of Maraviroc to HIV infected individuals were reviewed with emphasis on reported respiratory infections. We included in the analysis those studies enrolling more than 100 participants in the maraviroc treatment arm.

Results: We compared individuals treated with optimized background regimen plus placebo to those receiving the background regimen along with the CCR5 anatagonist maraviroc. We found in the clinical data significantly more respiratory infections in the CCR5 blocker treated arm than in the control arm.

Limitations: The studies had limited microbiological analysis of respiratory infections and the categorization differs between the studies included.

Conclusions: This observation suggests that the CCR5 blockade may lead to more infections caused by other viruses and respiratory pathogens in HIV infected patients and the incidence of such infections needs to be carefully assessed.