Patrick W Wright1, Ashmit Pyakurel, Florin F Vaida, Richard W Price, Evelyn Lee, Julia Peterson, Dietmar Fuchs, Henrik Zetterberg, Kevin R Robertson, Rudolph Walter, Dieter J Meyerhoff, Serena S Spudich, Beau M Ances. 1. aDepartment of Biomedical Engineering, WUSTL bDepartment of Neurology, WUSTL School of Medicine, St. Louis, Missouri cDepartment of Biomedical Engineering, Louisiana Tech University, Ruston, Louisiana dDepartment of Family Medicine and Public Health, UCSD, San Diego eDepartment of Neurology, UCSF, San Francisco, California, USA fDivision of Biological Chemistry, Innsbruck Medical University, Innsbruck, Austria gDivision of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden hDepartment of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK iDepartment of Neurology, UNC, Chapel Hill, North Carolina jCenter for Imaging of Neurodegenerative Diseases, VA Medical Center kDepartment of Radiology and Biomedical Imaging, UCSF, San Francisco, California lDepartment of Neurology, Yale University, New Haven, Connecticut, USA. *Serena S. Spudich and Beau M. Ances contributed equally to the writing of this article.
Abstract
OBJECTIVE: Little is known about the extent of cortical and subcortical volumetric alterations that may occur within the first year of HIV infection [primary HIV infection (PHI)]. DESIGN: We used structural MRI in this prospective cross-sectional neuroimaging study to determine the extent of volumetric changes in early HIV infection. METHODS: Cerebrospinal fluid, blood, neuropsychological testing, and structural T1 MRI scans were acquired from 18 HIV and 47 PHI age-matched antiretroviral-naïve male participants. Using FreeSurfer 5.1, volumetric measurements were obtained from the caudate, amygdala, corpus callosum, ventricles, putamen, thalamus, cortical white matter, and total gray matter. Regional volumes were compared groupwise and related to biomarkers in cerebrospinal fluid (viral load, neopterin, and neurofilament light chain), blood (viral load, CD4, and CD8 T-cell count), and neuropsychometric tests (digit-symbol, grooved pegboard, finger-tapping, and timed gait). RESULTS: A trend-level moderate reduction of putamen volume (P = 0.076, adjusted Cohen's d = 0.5 after controlling for age) was observed for PHI compared with HIV-uninfected individuals. Within the PHI group, putamen volume associated with CD4 cell count (P = 0.03), CD4/CD8 ratio (P = 0.045), infection duration (P = 0.009), and worsening psychomotor performance on the digit-symbol (P = 0.028), finger-tapping (P = 0.039), and timed gait (P = 0.009) tests. CONCLUSION: Our volumetric results suggest that the putamen is preferentially susceptible to early HIV-associated processes. Examining the natural course of early HIV infection longitudinally will allow for mapping of the trajectory of HIV-associated central nervous system changes, enabling creation of improved interventional strategies to potentially stabilize or reverse these observed structural changes.
OBJECTIVE: Little is known about the extent of cortical and subcortical volumetric alterations that may occur within the first year of HIV infection [primary HIV infection (PHI)]. DESIGN: We used structural MRI in this prospective cross-sectional neuroimaging study to determine the extent of volumetric changes in early HIV infection. METHODS: Cerebrospinal fluid, blood, neuropsychological testing, and structural T1 MRI scans were acquired from 18 HIV and 47 PHI age-matched antiretroviral-naïve male participants. Using FreeSurfer 5.1, volumetric measurements were obtained from the caudate, amygdala, corpus callosum, ventricles, putamen, thalamus, cortical white matter, and total gray matter. Regional volumes were compared groupwise and related to biomarkers in cerebrospinal fluid (viral load, neopterin, and neurofilament light chain), blood (viral load, CD4, and CD8 T-cell count), and neuropsychometric tests (digit-symbol, grooved pegboard, finger-tapping, and timed gait). RESULTS: A trend-level moderate reduction of putamen volume (P = 0.076, adjusted Cohen's d = 0.5 after controlling for age) was observed for PHI compared with HIV-uninfected individuals. Within the PHI group, putamen volume associated with CD4 cell count (P = 0.03), CD4/CD8 ratio (P = 0.045), infection duration (P = 0.009), and worsening psychomotor performance on the digit-symbol (P = 0.028), finger-tapping (P = 0.039), and timed gait (P = 0.009) tests. CONCLUSION: Our volumetric results suggest that the putamen is preferentially susceptible to early HIV-associated processes. Examining the natural course of early HIV infection longitudinally will allow for mapping of the trajectory of HIV-associated central nervous system changes, enabling creation of improved interventional strategies to potentially stabilize or reverse these observed structural changes.
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