title: Patterns of white matter injury in HIV infection after partial immune reconstitution: a DTI tract-based spatial statistics study.
abstract: HIV-infected individuals with severe immune suppression are more likely to develop HIV-associated neurocognitive disorders than those with preserved immune function. While partial immune reconstitution occurs in those with severe immune suppression after starting combined antiretroviral therapy, it is not established whether improvement in immune function reverses or prevents injury to the central nervous system (CNS). To address this question, 50 participants (nadir CD4 counts ≤ 200 cells/mm(3), on a stable antiretroviral regimen for at least 12 consecutive weeks prior to study) and 13 HIV negative participants underwent a comprehensive neurological evaluation followed by diffusion tensor imaging (DTI). Eighty-four percent of the 50 HIV participants were neurologically asymptomatic (HIVNA) and 16 % had mild cognitive impairment (HIVCI). Tract-based spatial statistics (TBSS) on DTI data revealed that mean diffusivity (MD) increased significantly in the posterior aspect of both hemispheres in HIVNA compared to controls. In HIVCI, compared to controls and HIVNA, increased MD extended to prefrontal areas. Fractional anisotropy decreased only in HIVCI, compared to either controls or HIVNA. Furthermore, DTI showed significant correlations to duration of HIV infection and significant associations with multiple cognitive domains. This study highlights that in partial immune reconstitution, injury to the CNS is present even in those that are neurologically asymptomatic and there are discrete spatial patterns of white matter injury in HIVNA subjects compared to HIVCI subjects. Our results also show that quantitative analysis of DTI using TBSS is a sensitive approach to evaluate HIV-associated white matter disease and thus valuable in monitoring central nervous system injury.
authors.affiliation: Department of Imaging Sciences, University of Rochester, Rochester, NY, USA.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhu
authors.forename: Jianhui
authors.initials: J
authors.lastname: Zhong
authors.forename: Rui
authors.initials: R
authors.lastname: Hu
authors.forename: Madalina
authors.initials: M
authors.lastname: Tivarus
authors.forename: Sven
authors.initials: S
authors.lastname: Ekholm
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Harezlak
authors.forename: Hernando
authors.initials: H
authors.lastname: Ombao
authors.forename: Bradford
authors.initials: B
authors.lastname: Navia
authors.forename: Ron
authors.initials: R
authors.lastname: Cohen
authors.forename: Giovanni
authors.initials: G
authors.lastname: Schifitto
mesh_terms: D015526:AIDS Dementia Complex / Q000276:immunology* / Q000473:pathology*; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D001921:Brain / Q000473:pathology; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009483:Neuropsychological Tests
chemical_list: D044966:Anti-Retroviral Agents