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Predictors of CNS injury as measured by proton magnetic resonance spectroscopy in the setting of chronic HIV infection and CART

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Abstract

The reasons for persistent brain dysfunction in chronically HIV-infected persons on stable combined antiretroviral therapies (CART) remain unclear. Host and viral factors along with their interactions were examined in 260 HIV-infected subjects who underwent magnetic resonance spectroscopy (MRS). Metabolite concentrations (NAA/Cr, Cho/Cr, MI/Cr, and Glx/Cr) were measured in the basal ganglia, the frontal white matter, and gray matter, and the best predictive models were selected using a bootstrap-enhanced Akaike information criterion (AIC). Depending on the metabolite and brain region, age, race, HIV RNA concentration, ADC stage, duration of HIV infection, nadir CD4, and/or their interactions were predictive of metabolite concentrations, particularly the basal ganglia NAA/Cr and the mid-frontal NAA/Cr and Glx/Cr, whereas current CD4 and the CPE index rarely or did not predict these changes. These results show for the first time that host and viral factors related to both current and past HIV status contribute to persisting cerebral metabolite abnormalities and provide a framework for further understanding neurological injury in the setting of chronic and stable disease.

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Conflict of interest

The authors, Harezlak J, Cohen R, Gongvatana A, Taylor M, Buchthal S, Schifitto G, Zhong J, Daar ES, Alger JR, Brown M, Singer EJ, Campbell TB, McMahon D, So YT, Yiannoutsos CT, and Navia BA, declare that they have no conflict of interest.

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Authors and Affiliations

  1. Indiana University Fairbanks School of Public Health, 410 W 10th St., Suite 3000, Indianapolis, IN, 46202, USA

    J. Harezlak & C. T. Yiannoutsos

  2. University of Florida College of Medicine, Gainesville, FL, USA

    R. Cohen

  3. University of California - San Diego School of Medicine, La Jolla, CA, USA

    A. Gongvatana & M. Taylor

  4. University of Hawaii, Honolulu, HI, USA

    S. Buchthal

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

    G. Schifitto & J. Zhong

  6. Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, University of California, Los Angeles, CA, USA

    E. S. Daar

  7. David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    J. R. Alger & E. J. Singer

  8. University of Colorado Denver, Aurora, CO, USA

    M. Brown & T. B. Campbell

  9. University of Pittsburgh, Pittsburgh, PA, USA

    D. McMahon

  10. Stanford University Medical Center, Palo Alto, CA, USA

    Y. T. So

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

    B. A. Navia

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  1. J. Harezlak
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  2. R. Cohen
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  3. A. Gongvatana
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  4. M. Taylor
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  5. S. Buchthal
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  6. G. Schifitto
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  7. J. Zhong
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  8. E. S. Daar
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  9. J. R. Alger
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  10. M. Brown
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  11. E. J. Singer
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  12. T. B. Campbell
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  13. D. McMahon
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  14. Y. T. So
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  15. C. T. Yiannoutsos
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  16. B. A. Navia
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The HIV Neuroimaging Consortium

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Correspondence to J. Harezlak.

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Sources: NIH grants NS36524, RR025780, U01MH083506, U01MH083500, NS038841, AI069424, and MH083506

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Harezlak, J., Cohen, R., Gongvatana, A. et al. Predictors of CNS injury as measured by proton magnetic resonance spectroscopy in the setting of chronic HIV infection and CART. J. Neurovirol. 20, 294–303 (2014). https://doi.org/10.1007/s13365-014-0246-6

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