Persistence of HIV-associated cognitive impairment, inflammation, and neuronal injury in era of highly active antiretroviral treatment.

Abstract

OBJECTIVE:

To determine whether cognitive impairment and brain injury as measured by proton magnetic resonance spectroscopy (MRS) persist in the setting of HAART.

DESIGN:

This study is an observational cohort study.

METHODS:

MRS was performed in 268 patients: HIV-negative controls (N = 28), HIV-positive neuroasymptomatic individuals (N = 124), and individuals with AIDS dementia complex (ADC; N = 50) on stable antiretroviral therapy (ART) with a mean duration of infection of 12 years and CD4 cell count of 309 cells/μl. Four metabolites were measured over creatine: N-acetyl aspartate (NAA), marker of neuronal integrity; choline (Cho), myoinositol, markers of inflammation, and glutamate and glutamine (Glx) in the basal ganglia, frontal white matter (FWM), and mid-frontal cortex. Analyses included analysis of variance, analysis of covariance, linear, and nonparametric regression models.

RESULTS:

Cognitive impairment was found in 48% of HIV-infected individuals. Both HIV-positive groups showed significant increases in myoinositol/creatine or Cho/creatine in all brain regions when compared to controls; a significant decrease in Glx/creatine in the FWM was observed in the neuroasymptomatic group; and only individuals with ADC showed a significant reduction in NAA/creatine, although a significant trend for decreasing NAA/creatine in the basal ganglia was found across the groups. Effects related to aging and duration of infection, but not central nervous system penetration effectiveness were observed.

CONCLUSION:

Brain inflammatory changes remain ubiquitous among HIV-infected individuals, whereas neuronal injury occurs predominantly in those with cognitive impairment. Together these findings indicate that despite the widespread use of HAART, HIV-associated cognitive impairment and brain injury persist in the setting of chronic and stable disease.

• Authors: Jarek Harezlak, Steven Buchthal, Michael Taylor, Giovanni Schifitto, Jianhui Zhong, Eric Daar, Jeffrey Alger, Elyse Singer, Thomas Campbell, Constantin Yiannoutsos, Ronald Cohen, Bradford Navia, HIV Neuroimaging Consortium
• Journal: AIDS (London, England) (AIDS) Vol. 25 Issue 5 Pg. 625-33 (Mar 13 2011) ISSN: 1473-5571 [Electronic] England
• PMID: 21297425 (Publication Type: Journal Article)

Topics

• AIDS Dementia Complex (drug therapy, epidemiology, metabolism)
• Antiretroviral Therapy, Highly Active
• Brain (pathology)
• CD4 Lymphocyte Count
• Female
• HIV Infections (drug therapy, metabolism, pathology)
• Humans
• Inflammation (diagnosis, metabolism)
• Magnetic Resonance Spectroscopy
• Male
• Middle Aged
• Treatment Outcome