title: Higher subcortical and white matter cerebral blood flow in perinatally HIV-infected children.
abstract: This study aimed to evaluate cerebral blood flow (CBF) in pediatric human immunodeficiency virus (HIV)-infection, and its role in HIV-related cerebral injury and cognitive impairment.This cross-sectional observational study compared 28 perinatally HIV-infected children (8-18 years) to 34 healthy controls matched for age, sex, ethnicity, and socio-economic status. All participants underwent 3-Tesla magnetic resonance imaging, using arterial spin labeling to assess CBF in gray matter (GM), white matter (WM), basal ganglia, and thalamus. We used linear regression analysis to evaluate group differences and associations with HIV disease and treatment characteristics, macrostructural (volume loss, WM lesions) or microstructural injury (increased WM diffusivity, neurometabolite alterations), or poorer cognitive performance.HIV-infected children had higher CBF in WM (+10.2%; P = 0.042), caudate nucleus (+4.8%; P = 0.002), putamen (+3.6%; P = 0.017), nucleus accumbens (+3.9%; P = 0.031), and thalamus (+5.5%; P = 0.032). Thalamus CBF was highest in children with a Centers for Disease Control and Prevention stage B (Coef. = 6.45; P = 0.005) or C (Coef. = 8.52; P = 0.001) diagnosis. Lower GM CBF was associated with higher WM lesion volume in HIV-infected children (Coef. = -0.053; P = 0.001). No further associations with HIV-related cognitive impairment or cerebral injury were found.CBF was higher in WM, basal ganglia, and thalamus in combination antiretroviral therapy (cART)-treated perinatally HIV-infected children, but this was not associated with cerebral injury or cognitive impairment. HIV-infected children with lower GM CBF had a higher volume of WM lesions, which could reflect vascular disease as potential contributing factor to white matter injury. Lifelong exposure to HIV and cART in this population warrants longitudinal assessment of CBF and how it relates to (neuro)inflammation, vascular dysfunction, and cerebral injury in pediatric HIV.
authors.affiliation: Department of Pediatric Hematology, Immunology and Infectious Diseases, Emma Children's Hospital/Academic Medical Center, University of Amsterdam Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Cognitive Neurology Research Unit, Sunnybrook Health Sciences Center, Toronto, Canada Department of Global Health, Academic Medical Center, University of Amsterdam, and Amsterdam Institute for Global Health and Development Department of Internal Medicine, Division of Infectious Diseases, Center for Infection and Immunity Amsterdam, Academic Medical Center HIV Monitoring Foundation, Amsterdam, The Netherlands.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Blokhuis
authors.forename: Henri J M M
authors.initials: HJMM
authors.lastname: Mutsaerts
authors.forename: Sophie
authors.initials: S
authors.lastname: Cohen
authors.forename: Henriëtte J
authors.initials: HJ
authors.lastname: Scherpbier
authors.forename: Matthan W A
authors.initials: MWA
authors.lastname: Caan
authors.forename: Charles B L M
authors.initials: CBLM
authors.lastname: Majoie
authors.forename: Taco W
authors.initials: TW
authors.lastname: Kuijpers
authors.forename: Peter
authors.initials: P
authors.lastname: Reiss
authors.forename: Ferdinand W N M
authors.initials: FWNM
authors.lastname: Wit
authors.forename: Dasja
authors.initials: D
authors.lastname: Pajkrt
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002560:Cerebrovascular Circulation; D002648:Child; D003071:Cognition; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology* / Q000523:psychology; D006801:Humans; D008297:Male; D066127:White Matter / Q000098:blood supply / Q000473:pathology