Journal of NeuroVirology

, Volume 19, Issue 3, pp 209–218

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

  • Assawin Gongvatana
  • Jaroslaw Harezlak
  • Steven Buchthal
  • Eric Daar
  • Giovanni Schifitto
  • Thomas Campbell
  • Michael Taylor
  • Elyse Singer
  • Jeffrey Algers
  • Jianhui Zhong
  • Mark Brown
  • Deborah McMahon
  • Yuen T. So
  • Deming Mi
  • Robert Heaton
  • Kevin Robertson
  • Constantin Yiannoutsos
  • Ronald A. Cohen
  • Bradford Navia
  • HIV Neuroimaging Consortium
Article

DOI: 10.1007/s13365-013-0162-1

Cite this article as:
Gongvatana, A., Harezlak, J., Buchthal, S. et al. J. Neurovirol. (2013) 19: 209. doi:10.1007/s13365-013-0162-1

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 infectionLongitudinal studyMRIMR spectroscopyCerebral metabolitesAntiretroviral therapy

Copyright information

© Journal of NeuroVirology, Inc. 2013

Authors and Affiliations

  • Assawin Gongvatana
    • 1
  • Jaroslaw Harezlak
    • 2
  • Steven Buchthal
    • 3
  • Eric Daar
    • 4
  • Giovanni Schifitto
    • 5
  • Thomas Campbell
    • 6
  • Michael Taylor
    • 7
  • Elyse Singer
    • 8
  • Jeffrey Algers
    • 8
  • Jianhui Zhong
    • 5
  • Mark Brown
    • 6
  • Deborah McMahon
    • 9
  • Yuen T. So
    • 10
  • Deming Mi
    • 2
  • Robert Heaton
    • 7
  • Kevin Robertson
    • 11
  • Constantin Yiannoutsos
    • 2
  • Ronald A. Cohen
    • 1
    • 14
  • Bradford Navia
    • 12
    • 13
  • HIV Neuroimaging Consortium
  1. 1.Brown University School of MedicineProvidenceUSA
  2. 2.Indiana University Fairbanks School of Public HealthIndianapolisUSA
  3. 3.University of HawaiiHonoluluUSA
  4. 4.Los Angeles Biomedical Research Institute at Harbor-UCLA Medical CenterTorranceUSA
  5. 5.University of Rochester School of MedicineRochesterUSA
  6. 6.University of Colorado Medical CenterDenverUSA
  7. 7.University of CaliforniaSan DiegoUSA
  8. 8.David Geffen School of MedicineUniversity of CaliforniaLos AngelesUSA
  9. 9.University of PittsburghPittsburghUSA
  10. 10.Stanford University School of MedicinePalo AltoUSA
  11. 11.University of North CarolinaChapel HillUSA
  12. 12.Tufts University School of MedicineBostonUSA
  13. 13.Department of Public Heath and Community Medicine, Tufts School of MedicineJaharis Family Center for Biomedical ResearchBostonUSA
  14. 14.Department of Aging-Geriatric ResearchUniversity of Florida College of MedicineGainesvilleUSA