title: Clinical factors related to brain structure in HIV: the CHARTER study.
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.
authors.affiliation: Department of Psychiatry, University of California, San Diego, 9500 Gilman Drive M/C 0115, La Jolla, CA, USA. tjernigan@ucsd.edu
authors.forename: Terry L
authors.initials: TL
authors.lastname: Jernigan
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Archibald
authors.forename: Christine
authors.initials: C
authors.lastname: Fennema-Notestine
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Taylor
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Theilmann
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Julaton
authors.forename: Randy J
authors.initials: RJ
authors.lastname: Notestine
authors.forename: Tanya
authors.initials: T
authors.lastname: Wolfson
authors.forename: Scott L
authors.initials: SL
authors.lastname: Letendre
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Ellis
authors.forename: Robert K
authors.initials: RK
authors.lastname: Heaton
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Gamst
authors.forename: Donald R
authors.initials: DR
authors.lastname: Franklin
authors.forename: David B
authors.initials: DB
authors.lastname: Clifford
authors.forename: Ann C
authors.initials: AC
authors.lastname: Collier
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Gelman
authors.forename: Christina
authors.initials: C
authors.lastname: Marra
authors.forename: Justin C
authors.initials: JC
authors.lastname: McArthur
authors.forename: J Allen
authors.initials: JA
authors.lastname: McCutchan
authors.forename: Susan
authors.initials: S
authors.lastname: Morgello
authors.forename: David M
authors.initials: DM
authors.lastname: Simpson
authors.forename: Igor
authors.initials: I
authors.lastname: Grant
mesh_terms: D015526:AIDS Dementia Complex / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000209:etiology / Q000473:pathology / Q000821:virology; D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000008:administration & dosage; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology / Q000821:virology; D002540:Cerebral Cortex / Q000473:pathology / Q000821:virology; D005260:Female; D006678:HIV / Q000502:physiology; D015658:HIV Infections / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000821:virology; D016174:Hepacivirus / Q000502:physiology; D006526:Hepatitis C / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000150:complications / Q000821:virology; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood / Q000134:cerebrospinal fluid; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D012367:RNA, Viral