Effect of hepatitis C virus on the central nervous system of HIV-infected individuals

Abstract

Correspondence: Daniel Forton Department of Gastroenterology and Hepatology, St George’s University of London, Blackshaw Road, London SW17 0QT, United Kingdom Tel +44 208 725 3520 Fax +44 208 725 3032 Email dforton@sgul.ac.uk Abstract: Infection with the human immunodeficiency virus (HIV) is associated with a spectrum of neuropsychiatric manifestations ranging from asymptomatic cognitive impairment, detectable only by sensitive neurocognitive tests, to overt HIV-associated dementia. Highly active antiretroviral therapy has led to significant reductions in the incidence of severe HIVassociated dementia. However, the overall prevalence of milder HIV-associated cognitive disorders appears to be increasing as HIV-infected subjects live longer in the era of combined antiretroviral treatments. Chronic hepatitis C virus (HCV) infection is also associated with neuropsychological symptoms and impaired cognitive performance in some patients, and recent evidence suggests that these central nervous system (CNS) symptoms may be caused by HCV entry into the brain via endothelial infection. Similarly to the neuropathological processes in HIV infection, microglial activation in HCV infected subjects may underlie the CNS metabolic abnormalities and impaired cognitive performance that have been described in studies of HCVinfected cohorts. A significant proportion of HIV-infected subjects are coinfected with HCV, but the impact and clinical importance of coinfection on cognitive function has only been addressed in a small number of research studies. There is some evidence that coinfection may adversely affect neurocognitive function; however, studies published thus far are limited by a number of confounding factors and small sample sizes. This article aims to review the current evidence examining neurocognitive function in HIVand HCV-monoinfection and further critically discusses previous studies that have explored the impact of coinfection with HCV on CNS function of HIV-infected cohorts. It is clear that, as the population of HIV-infected individuals ages and neurocognitive disorders persist in the post-combination antiretroviral treatment era, a better understanding of the neuropathological processes and improved characterization of deficits is required to allow development of better treatments. At the advent of interferon-free, directly acting antiviral therapies against HCV, this is increasingly important. The impact of CNS infection by these viruses remains poorly understood, both in terms of neurocognitive symptoms and as a potential mechanism for HCV virological relapse after treatment.