title: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.affiliation: Indiana University School of Medicine, Indianapolis, USA.
authors.forename: Jarek
authors.initials: J
authors.lastname: Harezlak
authors.forename: Steven
authors.initials: S
authors.lastname: Buchthal
authors.forename: Michael
authors.initials: M
authors.lastname: Taylor
authors.forename: Giovanni
authors.initials: G
authors.lastname: Schifitto
authors.forename: Jianhui
authors.initials: J
authors.lastname: Zhong
authors.forename: Eric
authors.initials: E
authors.lastname: Daar
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Alger
authors.forename: Elyse
authors.initials: E
authors.lastname: Singer
authors.forename: Thomas
authors.initials: T
authors.lastname: Campbell
authors.forename: Constantin
authors.initials: C
authors.lastname: Yiannoutsos
authors.forename: Ronald
authors.initials: R
authors.lastname: Cohen
authors.forename: Bradford
authors.initials: B
authors.lastname: Navia
mesh_terms: D015526:AIDS Dementia Complex / Q000188:drug therapy / Q000453:epidemiology* / Q000378:metabolism; D023241:Antiretroviral Therapy, Highly Active; D001921:Brain / Q000473:pathology*; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000175:diagnosis* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome