Article

Journal of NeuroVirology

, Volume 19, Issue 3, pp 209-218

First online:

Progressive cerebral injury in the setting of chronic HIV infection and antiretroviral therapy

  • Assawin GongvatanaAffiliated withBrown University School of Medicine
  • , Jaroslaw HarezlakAffiliated withIndiana University Fairbanks School of Public Health
  • , Steven BuchthalAffiliated withUniversity of Hawaii
  • , Eric DaarAffiliated withLos Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
  • , Giovanni SchifittoAffiliated withUniversity of Rochester School of Medicine
  • , Thomas CampbellAffiliated withUniversity of Colorado Medical Center
  • , Michael TaylorAffiliated withUniversity of California
  • , Elyse SingerAffiliated withDavid Geffen School of Medicine, University of California
  • , Jeffrey AlgersAffiliated withDavid Geffen School of Medicine, University of California
    • , Jianhui ZhongAffiliated withUniversity of Rochester School of Medicine
    • , Mark BrownAffiliated withUniversity of Colorado Medical Center
    • , Deborah McMahonAffiliated withUniversity of Pittsburgh
    • , Yuen T. SoAffiliated withStanford University School of Medicine
    • , Deming MiAffiliated withIndiana University Fairbanks School of Public Health
    • , Robert HeatonAffiliated withUniversity of California
    • , Kevin RobertsonAffiliated withUniversity of North Carolina
    • , Constantin YiannoutsosAffiliated withIndiana University Fairbanks School of Public Health
    • , Ronald A. CohenAffiliated withBrown University School of MedicineDepartment of Aging-Geriatric Research, University of Florida College of Medicine Email author 
    • , Bradford NaviaAffiliated withTufts University School of MedicineDepartment of Public Heath and Community Medicine, Tufts School of Medicine, Jaharis Family Center for Biomedical Research Email author 
    • , HIV Neuroimaging Consortium

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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.

Keywords

HIV infection Longitudinal study MRI MR spectroscopy Cerebral metabolites Antiretroviral therapy