Journal of NeuroVirology

, Volume 19, Issue 4, pp 393–401 | Cite as

Increases in brain white matter abnormalities and subcortical gray matter are linked to CD4 recovery in HIV infection

  • Christine Fennema-Notestine
  • Ronald J. Ellis
  • Sarah L. Archibald
  • Terry L. Jernigan
  • Scott L. Letendre
  • Randy J. Notestine
  • Michael J. Taylor
  • Rebecca J. Theilmann
  • Michelle D. Julaton
  • David J. Croteau
  • Tanya Wolfson
  • Robert K. Heaton
  • Anthony C. Gamst
  • Donald R. FranklinJr.
  • David B. Clifford
  • Ann C. Collier
  • Benjamin B. Gelman
  • Christina Marra
  • Justin C. McArthur
  • J. Allen McCutchan
  • Susan Morgello
  • David M. Simpson
  • Igor Grant
  • for the CHARTER Group
Article

Abstract

MRI alterations in the cerebral white (WM) and gray matter (GM) are common in HIV infection, even during successful combination antiretroviral therapy (CART), and their pathophysiology and clinical significance are unclear. We evaluated the association of these alterations with recovery of CD4+ T cells. Seventy-five HIV-infected (HIV+) volunteers in the CNS HIV Anti-Retroviral Therapy Effects Research study underwent brain MRI at two visits. Multi-channel morphometry yielded volumes of total cerebral WM, abnormal WM, cortical and subcortical GM, and ventricular and sulcal CSF. Multivariable linear regressions were used to predict volumetric changes with change in current CD4 and detectable HIV RNA. On average, the cohort (79 % initially on CART) demonstrated loss of total cerebral WM alongside increases in abnormal WM and ventricular volumes. A greater extent of CD4 recovery was associated with increases in abnormal WM and subcortical GM volumes. Virologic suppression was associated with increased subcortical GM volume, independent of CD4 recovery. These findings suggest a possible link between brain alterations and immune recovery, distinct from the influence of virologic suppression. The association of increasing abnormal WM and subcortical GM volumes with CD4+ T cell recovery suggests that neuroinflammation may be one mechanism in CNS pathogenesis.

Keywords

Antiretroviral therapy Brain CD4+ T cell Immune recovery/reconstitution Inflammation MRI 

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Copyright information

© Journal of NeuroVirology, Inc. 2013

Authors and Affiliations

  • Christine Fennema-Notestine
    • 1
    • 2
  • Ronald J. Ellis
    • 4
  • Sarah L. Archibald
    • 1
  • Terry L. Jernigan
    • 1
    • 2
  • Scott L. Letendre
    • 3
  • Randy J. Notestine
    • 1
  • Michael J. Taylor
    • 1
  • Rebecca J. Theilmann
    • 2
  • Michelle D. Julaton
    • 1
  • David J. Croteau
    • 4
  • Tanya Wolfson
    • 6
  • Robert K. Heaton
    • 1
  • Anthony C. Gamst
    • 5
  • Donald R. FranklinJr.
    • 1
  • David B. Clifford
    • 7
  • Ann C. Collier
    • 8
  • Benjamin B. Gelman
    • 10
  • Christina Marra
    • 8
    • 9
  • Justin C. McArthur
    • 11
  • J. Allen McCutchan
    • 3
  • Susan Morgello
    • 12
    • 13
  • David M. Simpson
    • 13
  • Igor Grant
    • 1
  • for the CHARTER Group
  1. 1.Department of PsychiatryUniversity of California, San DiegoLa JollaUSA
  2. 2.Department of RadiologyUniversity of California, San DiegoLa JollaUSA
  3. 3.Department of MedicineUniversity of California, San DiegoLa JollaUSA
  4. 4.Department of NeurosciencesUniversity of California, San DiegoLa JollaUSA
  5. 5.Biostatistics and BioinformaticsUniversity of California, San DiegoLa JollaUSA
  6. 6.Computational and Applied Statistics Laboratory (CASL)La JollaUSA
  7. 7.Department of NeurologyWashington University in St. LouisSt. LouisUSA
  8. 8.Department of MedicineUniversity of WashingtonSeattleUSA
  9. 9.Department of NeurologyUniversity of WashingtonSeattleUSA
  10. 10.Department of PathologyUniversity of Texas Medical BranchGalvestonUSA
  11. 11.Department of NeurologyJohns Hopkins UniversityBaltimoreUSA
  12. 12.Department of NeuroscienceMount Sinai School of MedicineNew YorkUSA
  13. 13.Department of NeurologyMount Sinai School of MedicineNew YorkUSA

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