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The Effect of Central Nervous System Penetration Effectiveness of Highly Active Antiretroviral Therapy on Neuropsychological Performance and Neuroimaging in HIV Infected Individuals

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Abstract

The incidence of HIV-associated dementia has been greatly reduced in the era of highly active antiretroviral therapy (HAART); however milder forms of cognitive impairment persist. It remains uncertain whether HAART regimens with a high degree of central nervous system penetration effectiveness (CPE) exert beneficial neurological outcomes in HIV-infected (HIV+) individuals on stable treatment. Sixty-four HIV-infected adults on HAART were assigned a CPE score using a published ranking system and divided into high (≥7; n = 35) and low (<7; n = 29) CPE groups. All participants completed neuropsychological testing in addition to structural neuroimaging. Neuropsychological tests included measures known to be sensitive to HIV with values converted into standardized scores (NPZ-4) based on published normative scores. A semi-automated methodology was utilized to assess brain volumetrics within cortical (grey and white matter) and subcortical (thalamus, caudate, putamen) regions of interest. Analyses assessed NPZ-4 and brain volumetric differences between HIV+ individuals with high and low CPE scores. No significant differences in brain integrity were observed between the two groups. Long-term HAART regimens with a high degree of CPE were not associated with significantly improved neuropsychological or neuroimaging outcomes in HIV+ adults. Results suggest that alternate mechanisms may potentially contribute to better neurological outcomes in the era of HAART.

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Acknowledgments

The content is solely the responsibility of the authors and does not necessarily represent the official view of the NIH.

Sources of Funding

Financial Support: Supported by the National Institute of Nursing Research (R01NR012907, R01NR012657, and R01NR014449 to B.M.A.); Grossman Chancellor’s Fellowship (M.O.); National Science Foundation IGERT (0548890 to M.O.), and the National Institute of Aging (R01 NS052420) (R.H.P.). Research was conducted and supported by the Washington University Institute of Clinical and Translational Sciences (UL1 TR000448 from the National Center for Advancing Translational Sciences (NCATS)).

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Authors and Affiliations

  1. Department of Psychology, University of Missouri- Saint Louis, Saint Louis, MO, USA

    Laurie M. Baker, Robert H. Paul, Jodi M. Heaps-Woodruff, Christina Usher & Sarah Cooley

  2. Department of Neurology, Washington University in Saint Louis School of Medicine, 660 South Euclid Avenue, Campus Box 8111, St. Louis, MO, 63110, USA

    Jee Yoon Chang, Mario Ortega, Zachary Margolin, Brian Basco & Beau M Ances

  3. Department of Radiology, Washington University in Saint Louis, Saint Louis, MO, USA

    Beau M Ances

  4. Department of Biomedical Engineering, Washington University in Saint Louis, Saint Louis, MO, USA

    Beau M Ances

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  1. Laurie M. Baker
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  2. Robert H. Paul
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  3. Jodi M. Heaps-Woodruff
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  4. Jee Yoon Chang
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  5. Mario Ortega
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  7. Christina Usher
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  9. Sarah Cooley
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  10. Beau M Ances
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Correspondence to Beau M Ances.

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Baker, L.M., Paul, R.H., Heaps-Woodruff, J.M. et al. The Effect of Central Nervous System Penetration Effectiveness of Highly Active Antiretroviral Therapy on Neuropsychological Performance and Neuroimaging in HIV Infected Individuals. J Neuroimmune Pharmacol 10, 487–492 (2015). https://doi.org/10.1007/s11481-015-9610-4

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  • DOI: https://doi.org/10.1007/s11481-015-9610-4

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