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

Research output: Contribution to journalArticle

46 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)209-218
Number of pages10
JournalJournal of NeuroVirology
Volume19
Issue number3
DOIs
StatePublished - Jun 2013

Fingerprint

Basal Ganglia
HIV Infections
Choline
Creatine
Wounds and Injuries
HIV
Brain
Frontal Lobe
Inositol
Therapeutics
Glutamine
Glutamic Acid
Magnetic Resonance Spectroscopy
N-acetylaspartate
White Matter

Keywords

  • Antiretroviral therapy
  • Cerebral metabolites
  • HIV infection
  • Longitudinal study
  • MR spectroscopy
  • MRI

ASJC Scopus subject areas

  • Virology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Neurology

Cite this

Progressive cerebral injury in the setting of chronic HIV infection and antiretroviral therapy. / Gongvatana, Assawin; Harezlak, Jaroslaw; Buchthal, Steven; Daar, Eric; Schifitto, Giovanni; Campbell, Thomas; Taylor, Michael; Singer, Elyse; Algers, Jeffrey; Zhong, Jianhui; Brown, Mark; McMahon, Deborah; So, Yuen T.; Mi, Deming; Heaton, Robert; Robertson, Kevin; Yiannoutsos, Constantin; Cohen, Ronald A.; Navia, Bradford.

In: Journal of NeuroVirology, Vol. 19, No. 3, 06.2013, p. 209-218.

Research output: Contribution to journalArticle

Gongvatana, A, Harezlak, J, Buchthal, S, Daar, E, Schifitto, G, Campbell, T, Taylor, M, Singer, E, Algers, J, Zhong, J, Brown, M, McMahon, D, So, YT, Mi, D, Heaton, R, Robertson, K, Yiannoutsos, C, Cohen, RA & Navia, B 2013, 'Progressive cerebral injury in the setting of chronic HIV infection and antiretroviral therapy', Journal of NeuroVirology, vol. 19, no. 3, pp. 209-218. https://doi.org/10.1007/s13365-013-0162-1
Gongvatana, Assawin ; Harezlak, Jaroslaw ; Buchthal, Steven ; Daar, Eric ; Schifitto, Giovanni ; Campbell, Thomas ; Taylor, Michael ; Singer, Elyse ; Algers, Jeffrey ; Zhong, Jianhui ; Brown, Mark ; McMahon, Deborah ; So, Yuen T. ; Mi, Deming ; Heaton, Robert ; Robertson, Kevin ; Yiannoutsos, Constantin ; Cohen, Ronald A. ; Navia, Bradford. / Progressive cerebral injury in the setting of chronic HIV infection and antiretroviral therapy. In: Journal of NeuroVirology. 2013 ; Vol. 19, No. 3. pp. 209-218.
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