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

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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.

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Authors and Affiliations

  1. Brown University School of Medicine, Providence, RI, USA

    Assawin Gongvatana & Ronald A. Cohen

  2. Indiana University Fairbanks School of Public Health, Indianapolis, IN, USA

    Jaroslaw Harezlak, Deming Mi & Constantin Yiannoutsos

  3. University of Hawaii, Honolulu, HI, USA

    Steven Buchthal

  4. Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA

    Eric Daar

  5. University of Rochester School of Medicine, Rochester, NY, USA

    Giovanni Schifitto & Jianhui Zhong

  6. University of Colorado Medical Center, Denver, CO, USA

    Thomas Campbell & Mark Brown

  7. University of California, San Diego, CA, USA

    Michael Taylor & Robert Heaton

  8. David Geffen School of Medicine, University of California, Los Angeles, CA, USA

    Elyse Singer & Jeffrey Algers

  9. University of Pittsburgh, Pittsburgh, PA, USA

    Deborah McMahon

  10. Stanford University School of Medicine, Palo Alto, CA, USA

    Yuen T. So

  11. University of North Carolina, Chapel Hill, NC, USA

    Kevin Robertson

  12. Tufts University School of Medicine, Boston, MA, USA

    Bradford Navia

  13. Department of Public Heath and Community Medicine, Tufts School of Medicine, Jaharis Family Center for Biomedical Research, 150 Harrison Ave, Boston, MA, 02111, USA

    Bradford Navia

  14. Department of Aging-Geriatric Research, University of Florida College of Medicine, Gainesville, FL, 32603, USA

    Ronald A. Cohen

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  1. Assawin Gongvatana
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  2. Jaroslaw Harezlak
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  3. Steven Buchthal
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  4. Eric Daar
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  5. Giovanni Schifitto
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  7. Michael Taylor
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  8. Elyse Singer
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  9. Jeffrey Algers
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  10. Jianhui Zhong
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  11. Mark Brown
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  12. Deborah McMahon
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  13. Yuen T. So
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  14. Deming Mi
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  15. Robert Heaton
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  16. Kevin Robertson
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  17. Constantin Yiannoutsos
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  18. Ronald A. Cohen
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  19. Bradford Navia
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HIV Neuroimaging Consortium

Corresponding authors

Correspondence to Ronald A. Cohen or Bradford Navia.

Additional information

Sources: R01NS036524, R24NS038841, UL1RR025780, U01MH083506, R01NS036524, UM1AI069424, R01MH083550, K99AA020235

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Gongvatana, A., Harezlak, J., Buchthal, S. et al. Progressive cerebral injury in the setting of chronic HIV infection and antiretroviral therapy. J. Neurovirol. 19, 209–218 (2013). https://doi.org/10.1007/s13365-013-0162-1

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  • DOI: https://doi.org/10.1007/s13365-013-0162-1

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