Clinical factors related to brain structure in HIV

The CHARTER study

Terry L. Jernigan, 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. Franklin, David B. Clifford, Ann C. Collier, Benjamin Gelman, Christina Marra, Justin C. McArthur, J. Allen McCutchan, Susan Morgello & 2 others David M. Simpson, Igor Grant

Research output: Contribution to journalArticle

106 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)248-257
Number of pages10
JournalJournal of NeuroVirology
Volume17
Issue number3
DOIs
StatePublished - Jun 2011

Fingerprint

HIV
Brain
Cerebrospinal Fluid
RNA
Immunosuppression
Hepatitis C Antibodies
Structural Models
Therapeutics
CD4 Lymphocyte Count
Coinfection
HIV Infections
White Matter
Linear Models
Cross-Sectional Studies
Magnetic Resonance Imaging
Research

Keywords

  • HIV
  • Immunospupression
  • MRI
  • Neuroimaging

ASJC Scopus subject areas

  • Virology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Neurology

Cite this

Jernigan, T. L., Archibald, S. L., Fennema-Notestine, C., Taylor, M. J., Theilmann, R. J., Julaton, M. D., ... Grant, I. (2011). Clinical factors related to brain structure in HIV: The CHARTER study. Journal of NeuroVirology, 17(3), 248-257. https://doi.org/10.1007/s13365-011-0032-7

Clinical factors related to brain structure in HIV : The CHARTER study. / Jernigan, Terry L.; Archibald, Sarah L.; Fennema-Notestine, Christine; Taylor, Michael J.; Theilmann, Rebecca J.; Julaton, Michelle D.; Notestine, Randy J.; Wolfson, Tanya; Letendre, Scott L.; Ellis, Ronald J.; Heaton, Robert K.; Gamst, Anthony C.; Franklin, Donald R.; Clifford, David B.; Collier, Ann C.; Gelman, Benjamin; Marra, Christina; McArthur, Justin C.; McCutchan, J. Allen; Morgello, Susan; Simpson, David M.; Grant, Igor.

In: Journal of NeuroVirology, Vol. 17, No. 3, 06.2011, p. 248-257.

Research output: Contribution to journalArticle

Jernigan, TL, Archibald, SL, Fennema-Notestine, C, Taylor, MJ, Theilmann, RJ, Julaton, MD, Notestine, RJ, Wolfson, T, Letendre, SL, Ellis, RJ, Heaton, RK, Gamst, AC, Franklin, DR, Clifford, DB, Collier, AC, Gelman, B, Marra, C, McArthur, JC, McCutchan, JA, Morgello, S, Simpson, DM & Grant, I 2011, 'Clinical factors related to brain structure in HIV: The CHARTER study', Journal of NeuroVirology, vol. 17, no. 3, pp. 248-257. https://doi.org/10.1007/s13365-011-0032-7
Jernigan TL, Archibald SL, Fennema-Notestine C, Taylor MJ, Theilmann RJ, Julaton MD et al. Clinical factors related to brain structure in HIV: The CHARTER study. Journal of NeuroVirology. 2011 Jun;17(3):248-257. https://doi.org/10.1007/s13365-011-0032-7
Jernigan, Terry L. ; Archibald, Sarah L. ; Fennema-Notestine, Christine ; Taylor, Michael J. ; Theilmann, Rebecca J. ; Julaton, Michelle D. ; Notestine, Randy J. ; Wolfson, Tanya ; Letendre, Scott L. ; Ellis, Ronald J. ; Heaton, Robert K. ; Gamst, Anthony C. ; Franklin, Donald R. ; Clifford, David B. ; Collier, Ann C. ; Gelman, Benjamin ; Marra, Christina ; McArthur, Justin C. ; McCutchan, J. Allen ; Morgello, Susan ; Simpson, David M. ; Grant, Igor. / Clinical factors related to brain structure in HIV : The CHARTER study. In: Journal of NeuroVirology. 2011 ; Vol. 17, No. 3. pp. 248-257.
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