Structural brain abnormalities in successfully treated HIV infection: associations with disease and cerebrospinal fluid biomarkers.
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
Background: Brain structural abnormalities have been reported in persons with HIV (PWH) on suppressive combination antiretroviral therapy (cART), but their pathophysiology remains unclear. Methods: We investigated factors associated with brain tissue volumes and white matter microstructure (fractional anisotropy) in 134 PWH on suppressive cART and 79 comparable HIV-negative controls, aged ≥45 years from the Co-morBidity in Relation to AIDS (COBRA) cohort, using multimodal neuroimaging and cerebrospinal fluid (CSF) biomarkers. Results: Compared to controls, PWH had lower grey matter volumes (-13.7 mL [95%-confidence interval -25.1, -2.2 mL]) and fractional anisotropy (-0.0073 [-0.012, -0.0024]), with the largest differences observed in those with prior clinical AIDS. Hypertension and CSF soluble CD14 concentration were associated with lower fractional anisotropy. These associations were independent of HIV serostatus (Pinteraction=0.32 and Pinteraction=0.59, respectively) and did not explain the greater abnormalities in brain structure in relation to HIV. Conclusions: The presence of lower grey matter volumes and more white matter microstructural abnormalities in well-treated PWH partly reflect a combination of historical effects of AIDS, as well as the more general influence of systemic factors such as hypertension and ongoing neuroinflammation. Additional mechanisms explaining the accentuation of brain structure abnormalities in treated HIV infection remain to be identified.
Date Issued
2017-10-24
Date Acceptance
2017-06-09
Citation
Journal of Infectious Diseases, 2017, 217 (1), pp.69-81
ISSN
0022-1899
Publisher
Oxford University Press (OUP)
Start Page
69
End Page
81
Journal / Book Title
Journal of Infectious Diseases
Volume
217
Issue
1
Copyright Statement
This is a pre-copyedited, author-produced PDF of an article accepted for publication in Journal of Infectious Diseases following peer review. The version of record [insert complete citation information here] is available online at: https://dx.doi.org/10.1093/infdis/jix553
Sponsor
Commission of the European Communities
Imperial College Healthcare NHS Trust- BRC Funding
Imperial College Healthcare NHS Trust- BRC Funding
Identifier
PII: 4563300
Grant Number
305522
RDC04 79560
RDC04
Subjects
HIV
biomarkers
cerebrospinal fluid
neurofilament light chain
neuroimaging
Publication Status
Published