TY - JOUR
T1 - Patterns of white matter injury in HIV infection after partial immune reconstitution
T2 - A DTI tract-based spatial statistics study
AU - Zhu, Tong
AU - Zhong, Jianhui
AU - Hu, Rui
AU - Tivarus, Madalina
AU - Ekholm, Sven
AU - Harezlak, Jaroslaw
AU - Ombao, Hernando
AU - Navia, Bradford
AU - Cohen, Ron
AU - Schifitto, Giovanni
PY - 2013/2/18
Y1 - 2013/2/18
N2 - 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/mm3, 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.
AB - 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/mm3, 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.
KW - Cognitive impairment
KW - Diffusion tensor imaging
KW - HIV infection
KW - White matter injury
UR - http://www.scopus.com/inward/record.url?scp=84873621960&partnerID=8YFLogxK
U2 - 10.1007/s13365-012-0135-9
DO - 10.1007/s13365-012-0135-9
M3 - Article
C2 - 23179680
AN - SCOPUS:84873621960
VL - 19
SP - 10
EP - 23
JO - Journal of NeuroVirology
JF - Journal of NeuroVirology
SN - 1355-0284
IS - 1
ER -