title: Two patterns of cerebral metabolite abnormalities are detected on proton magnetic resonance spectroscopy in HIV-infected subjects commencing antiretroviral therapy.
abstract: BACKGROUND
  Cerebral function impairment remains problematic in subjects with chronic human immunodeficiency virus (HIV) infection despite effective combination antiretroviral therapy (cART). Using cerebral proton magnetic resonance spectroscopy ((1)H MRS), we aimed to determine if abnormalities could be detected in neurologically asymptomatic HIV-infected subjects electively commencing cART.
  
  
  METHODS
  Therapy-naive, HIV-infected individuals and HIV-uninfected controls underwent (1)H MRS in several anatomical voxels including the mid-frontal grey matter (FGM) and right basal ganglia (RBG). Differences in cerebral metabolite ratios between groups and correlations between immune and virological status were assessed.
  
  
  RESULTS
  Forty-six subjects were recruited (26 HIV-infected and 20 control subjects). In the HIV-infected group, mean CD4+ count (SD, cells per microlitre) and plasma HIV RNA (SD, log10 copies per millilitre) were 192 (86) and 4.71 (0.64), respectively. Choline (Cho)/Creatine (Cr) and myoinositol (MI)/Cr ratios were significantly lower in the FGM in HIV-infected subjects compared to controls (0.67 (0.14) versus 0.88 (0.49), p = 0.036, and 0.94 (0.28) and 1.17 (0.26), p = 0.008, for Cho/Cr and MI/Cr, respectively) and Cho/Cr ratio associated with CD4+ lymphocyte count (p = 0.041). N-Acetyl-aspartate (NAA)/Cho ratio was significantly lower in the RBG in HIV-infected subjects compared to controls (2.27 (0.54) versus 2.63 (0.68), p = 0.002), and this was associated with greater plasma HIV RNA load (p = 0.014).
  
  
  CONCLUSIONS
  Two patterns of cerebral metabolite abnormalities were observed in HIV-infected subjects electively commencing cART. Greater inflammatory metabolite ratios (Cho/Cr and MI/Cr) associated with lower markers of peripheral immune markers (CD4+ lymphocyte count) in the FGM and lower neuronal metabolite ratios (NAA/Cho) associated with greater HIV viraemia in the RBG were present in HIV-infected subjects.
authors: St. Mary's Hospital, Imperial College London, Ground Floor, Clinical Trials, Winston Churchill Wing, Praed Street, London, W2 1NY, UK. a.winston@imperial.ac.uk
authors: Alan
authors: A
authors: Winston
authors: Chris
authors: C
authors: Duncombe
authors: Patrick C K
authors: PC
authors: Li
authors: John M
authors: JM
authors: Gill
authors: Stephen J
authors: SJ
authors: Kerr
authors: Rebekah L
authors: RL
authors: Puls
authors: Simon D
authors: SD
authors: Taylor-Robinson
authors: Sean
authors: S
authors: Emery
authors: David A
authors: DA
authors: Cooper
mesh_terms: D015526:AIDS Dementia Complex / Q000188:drug therapy / Q000378:metabolism*; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001923:Brain Chemistry; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D005260:Female; D006801:Humans; D007294:Inositol / Q000378:metabolism; D016014:Linear Models; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; D001224:Aspartic Acid; D007294:Inositol; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline