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Safety concerns about CCR5 as an antiviral target

Telenti, Amalio

Current Opinion in HIV and AIDS: March 2009 - Volume 4 - Issue 2 - p 131–135
doi: 10.1097/COH.0b013e3283223d76
Entry inhibitors: Edited by Jose A. Esté

Purpose of review Clinical trials of CCR5 antagonists attest to their efficacy and tolerance in HIV treatment. However, there has been debate on their long-term safety because of the role of CCR5 in innate immunity. This review highlights gaps in our understanding of epidemiology of infections that are modulated by CCR5, in particular, in HIV-infected individuals.

Recent findings In the mouse model, CCR5 has a role in the response against pathogens as diverse as Toxoplama gondii, West Nile virus, Mycobacterium tuberculosis, herpes simplex virus, Trypanosoma cruzi, Cryptococcus neoformans, Chlamydia trachomatis, Listeria, and plasmodia. In human cohorts, individuals carrying the defective CCR5Δ32 allele present an increased susceptibility to flavivirus (West Nile virus and tickborne encephalitis virus). The selective pressures that led to the spread of loss-of-function CCR5 mutations in humans (CCR5Δ32), and in mangabeys (CCR5Δ24) are not understood.

Summary The recent availability of CCR5 antagonists has raised concern that genetic, biological, or chemical CCR5 knockout, although beneficial against some pathogens (i.e. HIV), could be deleterious for other processes implicated in pathogen response. The consequences of long-term pharmaceutical intervention on CCR5 should be carefully assessed through rigorous postmarketing surveillance.

Institute of Microbiology, University Hospital Center, University of Lausanne, Lausanne, Switzerland

Correspondence to Amalio Telenti, Institute of Microbiology, CHUV, 1011 Lausanne, Switzerland Tel: +41 21 314 0550; e-mail: Amalio.Telenti@chuv.ch

© 2009 Lippincott Williams & Wilkins, Inc.