title: Effects of nadir CD4 count and duration of human immunodeficiency virus infection on brain volumes in the highly active antiretroviral therapy era.
abstract: Cerebral atrophy is a well-described, but poorly understood complication of human immunodeficiency virus (HIV) infection. Despite reduced prevalence of HIV-associated dementia in the highly active antiretroviral therapy (HAART) era, HIV continues to affect the brains of patients with chronic infection. In this study we examine patterns of brain volume loss in HIV-infected patients on HAART, and demographic and clinical factors contributing to brain volume loss. We hypothesized that nadir CD4+ lymphocyte count, duration of HIV infection, and age would be associated with reduced cortical volumes. Volumes of cortical and subcortical regions in 69 HIV-infected neuroasymptomatic (NA) individuals and 13 with at least mild acquired immunodeficiency syndrome (AIDS) dementia complex (ADC) were measured using voxel-based morphometry. Demographic and clinical factors (age, plasma HIV RNA level, current and nadir CD4 counts, duration of infection, central nervous system [CNS] penetration of antiretroviral regimen) along with their interactions were entered into a regression model selection algorithm to determine the final models that best described regional brain volumes. Relative to NA, individuals with ADC exhibited decreased total gray matter and parietal cortex volumes and increased total ventricular volumes. Final regression models showed overall cerebral volume, including gray and white matter volume and volumes of the parietal, temporal, and frontal lobes and the hippocampus, were most strongly associated with disease history factors (nadir CD4 and duration of infection). In contrast, basal ganglia volumes were related most strongly to current disease factors, most notably plasma HIV RNA. These findings indicate that individuals with a history of chronic HIV infection with previous episodes of severely impaired immune function, as reflected by reduced nadir CD4+ lymphocyte count, may be at greatest risk for cerebral atrophy. The pattern of HIV-associated brain loss may be changing from a subcortical to a cortical disease among patients who are largely asymptomatic on HAART.
authors.affiliation: Department of Psychiatry and Human Behavior and the Brain Science Program, Brown University School of Medicine, Providence, RI 02903, USA. rcohen@lifespan.org
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Cohen
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Harezlak
authors.forename: Giovanni
authors.initials: G
authors.lastname: Schifitto
authors.forename: George
authors.initials: G
authors.lastname: Hana
authors.forename: Uraina
authors.initials: U
authors.lastname: Clark
authors.forename: Assawin
authors.initials: A
authors.lastname: Gongvatana
authors.forename: Robert
authors.initials: R
authors.lastname: Paul
authors.forename: Michael
authors.initials: M
authors.lastname: Taylor
authors.forename: Paul
authors.initials: P
authors.lastname: Thompson
authors.forename: Jeffery
authors.initials: J
authors.lastname: Alger
authors.forename: Mark
authors.initials: M
authors.lastname: Brown
authors.forename: Jianhui
authors.initials: J
authors.lastname: Zhong
authors.forename: Thomas
authors.initials: T
authors.lastname: Campbell
authors.forename: Elyse
authors.initials: E
authors.lastname: Singer
authors.forename: Eric
authors.initials: E
authors.lastname: Daar
authors.forename: Deborah
authors.initials: D
authors.lastname: McMahon
authors.forename: Yuen
authors.initials: Y
authors.lastname: Tso
authors.forename: Constantin T
authors.initials: CT
authors.lastname: Yiannoutsos
authors.forename: Bradford
authors.initials: B
authors.lastname: Navia
mesh_terms: D015526:AIDS Dementia Complex / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D000328:Adult; D000367:Age Factors; D023241:Antiretroviral Therapy, Highly Active; D001921:Brain / Q000187:drug effects / Q000473:pathology* / Q000821:virology; D018791:CD4 Lymphocyte Count; D003198:Computer Simulation; D005260:Female; D006678:HIV; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009929:Organ Size; D013997:Time Factors; D019562:Viral Load