A Longitudinal Analysis of Cerebral Blood Flow in Perinatally HIV Infected Adolescents as Compared to Matched Healthy Controls.

Jason G Van Genderen,Anne Marleen Ter Haar,Malon Van Den Hof,Vera C Keil,Dasja Pajkrt,Henk J M M Mutsaerts,Charlotte Blokhuis

doi:10.3390/v13112179

Abstract

Despite effective combination anti-retroviral therapy (cART), perinatally HIV infected (PHIV) adolescents still experience cognitive complications. We previously reported higher cerebral blood flow (CBF) in basal ganglia and white matter (WM) in PHIV children compared to matched controls. In healthy children CBF is associated with cognitive domains. To determine longitudinal changes in CBF and its impact on cognitive complications, we measured CBF—using arterial spin labeling—in 21 PHIV adolescents and 23 controls matched for age, sex and socio-economic status twice with a mean follow-up of 4.6 years. We explored associations between CBF changes and WM micro- and macrostructural markers and cognitive domains using linear mixed models. The median age at follow-up was comparable between PHIV adolescents 17.4y (IQR:15.3–20.7) and controls 16.2y (IQR:15.6–19.1). At baseline, PHIV had higher CBF in the caudate nucleus and putamen. CBF development was comparable in gray matter (GM), WM and subcortical regions in both groups. In our cohort, we found that over time an increase of GM CBF was associated with an increase of visual motor function (p = 0.043) and executive function (p = 0.045). Increase of CBF in the caudate nucleus, putamen and thalamus was associated with an increase processing speed (p = 0.033; 0.036; 0.003 respectively) and visual motor function (p = 0.023; 0.045; 0.003 respectively). CBF development is relatively normal in PHIV adolescents on cART. CBF decline is associated with cognitive impairment, irrespective of HIV status.

Highlights

The introduction of effective combination antiretroviral therapy has led to an increase of the life expectancy of perinatally human immunodeficiency virus (HIV)infected (PHIV) adolescents [1]
We excluded 1 PHIV and 3 controls from magnetic resonance imaging (MRI) analyses due to poor Arterial spin labeling (ASL) scan quality caused by head motion
The median age at the second enrollment was similar between PHIV adolescents (17.4 (IQR: 15.3–20.7)) and controls (16.2 (IQR: 15.6–19.1))

Summary

Introduction

The introduction of effective combination antiretroviral therapy (cART) has led to an increase of the life expectancy of perinatally human immunodeficiency virus (HIV)infected (PHIV) adolescents [1]. Despite these effective therapies, there is growing evidence suggesting that PHIV children and adolescents have an altered brain structure and function compared to HIV uninfected peers [2]. In PHIV children, functional brain changes include altered cerebral blood flow (CBF) compared to matched controls, suggesting possible vascular disease [4]. Some cross-sectional studies report a higher prevalence of white matter (WM) macro- and microstructural damage—i.e., WMH and increased white matter diffusivity—in PHIV children and adolescents compared to (matched) controls [7,8,9,10,11], this could not consistently be replicated in a longitudinal study [12]

Methods

Results

Conclusion