Perinatal HIV Infection or Exposure Is Associated With Low N-Acetylaspartate and Glutamate in Basal Ganglia at Age 9 but Not 7 Years.

Frances C Robertson,Mark F Cotton,Barbara Laughton,Martha J Holmes,Els Dobbels,André J W Van Der Kouwe,Ernesta M Meintjes,Francesca Little

doi:10.3389/fnhum.2018.00145

Abstract

Abnormalities of the basal ganglia are frequently seen in HIV-infected (HIV+) children despite antiretroviral treatment (ART) initiation during childhood. Assessment of metabolites associated with neuronal integrity or with glial proliferation can present a sensitive description of metabolic events underlying basal ganglia structural changes. We used magnetic resonance spectroscopy to examine differences in creatine, choline, N-acetylaspartate (NAA), glutamate, and myo-inositol between HIV+ children and HIV-unexposed controls, as well as between HIV-exposed uninfected (HEU) children and HIV-unexposed controls at age 7 and at age 9. No differences in metabolites relative to the HIV-unexposed control group were found at age 7. However, at 9 years, both HIV+ and HEU had lower NAA and glutamate than unexposed control children. HEU children also had lower creatine and choline than control children. At age 7, lower CD4/CD8 ratio at enrollment was associated with lower choline levels. At age 9 lower CD4/CD8 at enrollment was associated with lower myo-inositol. Low NAA and glutamate at age 9, but not 7, suggest that basal ganglia neurons may be particularly affected by perinatal HIV/ART and that neuronal damage may be ongoing despite early ART and viral suppression. Reduced basal ganglia metabolite levels in HEU children suggest an effect of HIV exposure on childhood brain development that merits further investigation using neuroimaging and neurocognitive testing.

Highlights

Infants with perinatal HIV infection can expect to survive childhood, they face life-long treatment with antiretrovirals (ARVs) in order to maintain a healthy immune system
Abnormalities of the basal ganglia are frequently seen in HIV-infected (HIV+) children and adults (George et al, 2009; Hoare et al, 2014), and subcortical structures may contain the highest levels of the virus (Tornatore et al, 1994)
This study presents single voxel spectroscopy (SVS) basal ganglia neurometabolite data in a larger sample of older HIV+ children than previously studied, 91% of whom had undetectable viral loads at 7 and 97% at 9 years, and all of whom had started antiretroviral treatment (ART) before 76 weeks of age

Summary

Introduction

Infants with perinatal HIV infection can expect to survive childhood, they face life-long treatment with antiretrovirals (ARVs) in order to maintain a healthy immune system. Starting antiretroviral therapy (ART) before 3 months of age yields good clinical, immunological, and developmental outcomes It is known that ART cannot completely reverse the neurological effects of HIV (Laughton et al, 2013; van Arnhem et al, 2013; Whitehead et al, 2014) and neurodevelopmental delay and neurocognitive deficits remain (Govender et al, 2011; Donald et al, 2014; Wilmshurst et al, 2014; Musielak and Fine, 2015). Neuroimaging shows that HIV+ children may have shape and volume alterations in subcortical gray matter (Lewis-de los Angeles et al, 2016; Yadav et al, 2017) and calcification of the basal ganglia (Govender et al, 2011), despite ART initiation during childhood

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