title: Progressive cerebral injury in the setting of chronic HIV infection and antiretroviral therapy.
abstract: Emerging evidence suggests that CNS injury and neurocognitive impairment persist in the setting of chronic HIV infection and combination antiretroviral therapy (CART). Yet, whether neurological injury can progress in this setting remains uncertain. Magnetic resonance spectroscopy and neurocognitive and clinical assessments were performed over 2 years in 226 HIV-infected individuals on stable CART, including 138 individuals who were neurocognitively asymptomatic (NA). Concentrations of N-acetylaspartate (NAA), creatine (Cr), choline (Cho), myoinositol, and glutamate/glutamine (Glx) were measured in the midfrontal cortex (MFC), frontal white matter (FWM), and basal ganglia (BG). Longitudinal changes in metabolite levels were determined using linear mixed effect models, as were metabolite changes in relation to global neurocognitive function. HIV-infected subjects showed significant annual decreases in brain metabolite levels in all regions examined, including NAA (2.95 %) and Cho (2.61 %) in the FWM; NAA (1.89 %), Cr (1.84 %), Cho (2.19 %), and Glx (6.05 %) in the MFC; and Glx (2.80 %) in the BG. Similar metabolite decreases were observed in the NA and subclinically impaired subgroups, including subjects with virologic suppression in plasma and CSF. Neurocognitive decline was associated with longitudinal decreases in Glx in the FWM and the BG, and in NAA in the BG. Widespread progressive changes in the brain, including neuronal injury, occur in chronically HIV-infected persons despite stable antiretroviral treatment and virologic suppression and can lead to neurocognitive declines. The basis for these findings is poorly understood and warrants further study.
authors.affiliation: Brown University School of Medicine, Providence, RI, USA.
authors.forename: Assawin
authors.initials: A
authors.lastname: Gongvatana
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Harezlak
authors.forename: Steven
authors.initials: S
authors.lastname: Buchthal
authors.forename: Eric
authors.initials: E
authors.lastname: Daar
authors.forename: Giovanni
authors.initials: G
authors.lastname: Schifitto
authors.forename: Thomas
authors.initials: T
authors.lastname: Campbell
authors.forename: Michael
authors.initials: M
authors.lastname: Taylor
authors.forename: Elyse
authors.initials: E
authors.lastname: Singer
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Algers
authors.forename: Jianhui
authors.initials: J
authors.lastname: Zhong
authors.forename: Mark
authors.initials: M
authors.lastname: Brown
authors.forename: Deborah
authors.initials: D
authors.lastname: McMahon
authors.forename: Yuen T
authors.initials: YT
authors.lastname: So
authors.forename: Deming
authors.initials: D
authors.lastname: Mi
authors.forename: Robert
authors.initials: R
authors.lastname: Heaton
authors.forename: Kevin
authors.initials: K
authors.lastname: Robertson
authors.forename: Constantin
authors.initials: C
authors.lastname: Yiannoutsos
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Cohen
authors.forename: Bradford
authors.initials: B
authors.lastname: Navia
mesh_terms: D015526:AIDS Dementia Complex / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D002794:Choline / Q000378:metabolism; D003071:Cognition / Q000502:physiology; D018450:Disease Progression; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006678:HIV / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007294:Inositol / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests
chemical_list: D019380:Anti-HIV Agents; D001224:Aspartic Acid; D018698:Glutamic Acid; D007294:Inositol; C000179:N-acetylaspartate; D002794:Choline