title: Neuronal-Glia Markers by Magnetic Resonance Spectroscopy in HIV Before and After Combination Antiretroviral Therapy.
abstract: OBJECTIVE
  Combination antiretroviral therapy (cART) can suppress plasma HIV RNA to undetectable levels; yet reports indicate persistent HIV-associated neurocognitive disorders (HAND) among treated individuals. We sought to investigate imaging correlates of incomplete cognitive recovery among individuals with chronic HIV.
  
  
  METHODS
  We used single voxel proton magnetic resonance spectroscopy in 4 regions of the brain to measure changes in neuronal and glia biomarkers in cART-naive subjects before (n = 59, 27 with HAND) and after 12 months of cART.
  
  
  RESULTS
  At baseline, we observed elevated total choline (CHO) in the basal ganglia (BG, P = 0.002) and in the posterior cingulate gyrus (PCG, P = 0.022) associated with HIV infection. Myo-inositol (MI) was elevated in the frontal white matter (FWM, P = 0.040). N-acetylaspartate was elevated in the BG (P = 0.047). Using a mixed model approach among all HIV-infected individuals, at 6 months, we observed decreased n- acetylaspartate in FWM (P = 0.031), decreased creatine in PCG (P = 0.026) and increased MI in frontal gray matter (FGM, P = 0.023). At 12 months, we observed an increase in BG MI (P = 0.038) and in FGM (P = 0.021). Compared to those with normal cognition, HAND cases had higher FGM MI (P = 0.014) at baseline. At 12 months, individuals that remained cognitively impaired compared with those without HAND exhibited elevated CHO in the PCG (P = 0.018) and decreased glutamate in both FWM (P = 0.027) and BG (P = 0.013).
  
  
  CONCLUSIONS
  cART started during chronic HIV is associated with reduced neuronal-glia and inflammatory markers. Alterations in CHO are noted among individuals who remain impaired after 12 months of cART.
authors.affiliation: *Department of Tropical Medicine, University of Hawaii, Honolulu, HI;†U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD;‡Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD;§SEARCH, Thai Red Cross AIDS Research Center, Bangkok, Thailand;‖Department of Radiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand;¶Division of Neurology, Department of Medicine, Phramongkutklao Hospital, Bangkok, Thailand;#Queen Savang Vadhana Memorial Hospital, Chomburi, Thailand;**Taksin Hospital, Bangkok, Thailand;††Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA; and‡‡Department of Psychology, Missouri Institute of Mental Health, University of Missouri, St. Louis, MO.
authors.forename: Napapon
authors.initials: N
authors.lastname: Sailasuta
authors.forename: Jintanat
authors.initials: J
authors.lastname: Ananworanich
authors.forename: Sukalaya
authors.initials: S
authors.lastname: Lerdlum
authors.forename: Pasiri
authors.initials: P
authors.lastname: Sithinamsuwan
authors.forename: James L K
authors.initials: JL
authors.lastname: Fletcher
authors.forename: Somporn
authors.initials: S
authors.lastname: Tipsuk
authors.forename: Mantana
authors.initials: M
authors.lastname: Pothisri
authors.forename: Tanate
authors.initials: T
authors.lastname: Jadwattanakul
authors.forename: Supunnee
authors.initials: S
authors.lastname: Jirajariyavej
authors.forename: Thep
authors.initials: T
authors.lastname: Chalermchai
authors.forename: Stephanie
authors.initials: S
authors.lastname: Catella
authors.forename: Edgar
authors.initials: E
authors.lastname: Busovaca
authors.forename: Akash
authors.initials: A
authors.lastname: Desai
authors.forename: Robert
authors.initials: R
authors.lastname: Paul
authors.forename: Victor
authors.initials: V
authors.lastname: Valcour
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002794:Choline / Q000378:metabolism; D003072:Cognition Disorders / Q000209:etiology / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; D001224:Aspartic Acid; C000179:N-acetylaspartate; D002794:Choline