Telenti A. Safety concerns about CCR5 as an antiviral target. Curr Opin HIV AIDS.

Telenti A. Safety concerns about CCR5 as an antiviral target. Curr Opin HIV AIDS.

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. 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 CCR5Delta32 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 (CCR5Delta32), and in mangabeys (CCR5Delta24) are not understood. 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.

CCR5 delta 32 deletion appears to make people less likely to acquire HIV infection (if homozygous) and more likely to have slower HIV disease progression (if heterozygous), we do not know if interfering with this receptor’s function pharmacologically with entry inhibitors that are CCR5 antagonists, such as maraviroc and vicriviroc, will have the same effects as congenital absence of the receptor. Because CCR5 appears to play a role in innate immunity against diverse diseases including trypanosomiasis, West Nile virus infection, malaria, and tick-borne encephalitis, it makes sense for people on CCR5 antagonists to limit their exposure to mosquitoes, ticks, and other biting insects until further information becomes available – we should all be trying to do this anyway.