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Clinical factors related to brain structure in HIV: the CHARTER study

  • Terry L. JerniganEmail author
  • Sarah L. Archibald
  • Christine Fennema-Notestine
  • Michael J. Taylor
  • Rebecca J. Theilmann
  • Michelle D. Julaton
  • Randy J. Notestine
  • Tanya Wolfson
  • Scott L. Letendre
  • Ronald J. Ellis
  • 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

Despite the widening use of combination antiretroviral therapy (ART), neurocognitive impairment remains common among HIV-infected (HIV+) individuals. Associations between HIV-related neuromedical variables and magnetic resonance imaging indices of brain structural integrity may provide insight into the neural bases for these symptoms. A diverse HIV+ sample (n = 251) was studied through the CNS HIV Antiretroviral Therapy Effects Research initiative. Multi-channel image analysis produced volumes of ventricular and sulcal cerebrospinal fluid (CSF), cortical and subcortical gray matter, total cerebral white matter, and abnormal white matter. Cross-sectional analyses employed a series of multiple linear regressions to model each structural volume as a function of severity of prior immunosuppression (CD4 nadir), current CD4 count, presence of detectable CSF HIV RNA, and presence of HCV antibodies; secondary analyses examined plasma HIV RNA, estimated duration of HIV infection, and cumulative exposure to ART. Lower CD4 nadir was related to most measures of the structural brain damage. Higher current CD4, unexpectedly, correlated with lower white and subcortical gray and increased CSF. Detectable CSF HIV RNA was related to less total white matter. HCV coinfection was associated with more abnormal white matter. Longer exposure to ART was associated with lower white matter and higher sulcal CSF. HIV neuromedical factors, including lower nadir, higher current CD4 levels, and detectable HIV RNA, were associated with white matter damage and variability in subcortical volumes. Brain structural integrity in HIV likely reflects dynamic effects of current immune status and HIV replication, superimposed on residual effects associated with severe prior immunosuppression.

Keywords

HIV MRI Neuroimaging Immunospupression 

Notes

Funding/Support

The CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) is supported by award N01 MH22005 from the National Institutes of Health.

Disclaimer

The views expressed in this article are those of the authors and do not reflect the official policy or position of the United States Government.

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Copyright information

© Journal of NeuroVirology, Inc. 2011

Authors and Affiliations

  • Terry L. Jernigan
    • 1
    • 2
    Email author
  • Sarah L. Archibald
    • 1
  • Christine Fennema-Notestine
    • 1
    • 2
  • Michael J. Taylor
    • 1
  • Rebecca J. Theilmann
    • 2
  • Michelle D. Julaton
    • 1
  • Randy J. Notestine
    • 1
  • Tanya Wolfson
    • 6
  • Scott L. Letendre
    • 3
  • Ronald J. Ellis
    • 4
  • 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
  • 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.Department of Biostatistics and BioinformaticsUniversity of California, San DiegoLa JollaUSA
  6. 6.Computational and Applied Statistics Laboratory (CASL)San Diego Supercomputer Center (SDSC)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 PathologyMount Sinai School of MedicineNew YorkUSA
  13. 13.Department of NeurologyMount Sinai School of MedicineNew YorkUSA

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