Cortical structural changes related to early antiretroviral therapy (ART) interruption in perinatally HIV-infected children at 5 years of age

Emmanuel C Nwosu; Martha J Holmes; Mark F Cotton; Els Dobbels; Francesca Little; Barbara Laughton; Andre van der Kouwe; Ernesta M Meintjes; Frances Robertson

doi:10.1016/j.ibneur.2021.02.001

Cortical structural changes related to early antiretroviral therapy (ART) interruption in perinatally HIV-infected children at 5 years of age

IBRO Neurosci Rep. 2021 Feb 10:10:161-170. doi: 10.1016/j.ibneur.2021.02.001. eCollection 2021 Jun.

Authors

Emmanuel C Nwosu^{1

2}, Martha J Holmes^{1

2}, Mark F Cotton³, Els Dobbels³, Francesca Little⁴, Barbara Laughton³, Andre van der Kouwe^{5

6}, Ernesta M Meintjes^{1

2}, Frances Robertson^{1

2}

Affiliations

¹ UCT Medical Imaging Research Unit, Division of Biomedical Engineering, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, South Africa.
² Neuroscience Institute, Faculty of Health Sciences, University of Cape Town, South Africa.
³ Family Centre for Research with Ubuntu, Department of Paediatrics & Child Health, Tygerberg Children's Hospital and Faculty of Health Sciences, Stellenbosch University, Cape Town, South Africa.
⁴ Department of Statistical Sciences, Faculty of Sciences, University of Cape Town, South Africa.
⁵ A.A. Martinos Centre for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA.
⁶ Department of Radiology, Harvard Medical School, Boston, MA, USA.

Abstract

ART interruption in children can occur especially in resource-limited settings for reasons including poor adherence, stock-outs, ART intolerance of non-pediatric formulas and pill size, as well as ultimately to test for HIV remission. Although early ART initiation is now standard of care in pediatric HIV management, very little is known on the effect of early ART initiation or subsequent interruption on brain development. This study aimed to investigate the effect of ART interruption on brain cortical thickness (CT) and folding in a subset of children from the Children with HIV Early antiRetroviral therapy (CHER) trial cohort who all started ART before 18 months of age. CHER participants in the neuroimaging follow-up study had magnetic resonance (MRI) scans on a 3T Siemens Allegra brain scanner at age 5.44 ± 0.37 years. MR images were processed using the automated cross-sectional stream in FreeSurfer v6.0 and vertex wise comparisons of CT and local gyrification indices (LGIs) were performed between HIV+ children and HIV- controls, as well as between HIV+ children on interrupted or continuous ART and controls. HIV+ children (n = 46) showed thicker cortex than HIV- children (n = 29) in bilateral frontal and left temporo-insular regions but lower LGIs in left superior and bilateral medial orbitofrontal cortex extending into rostral anterior cingulate. Children on interrupted ART (n = 21) had thicker cortex than HIV- controls in left frontal and right insular regions, but children on continuous treatment (n = 25) showed no difference from controls. Children on both interrupted and continuous ART showed region-specific alterations in LGI relative to controls. Cortical folding appears more sensitive than CT to early life events including early ART and interruption. However, immune health resilience in children can translate to long term preservation of morphometric brain development, especially for those on early and continuous treatment.

Keywords: ART interruption; Brain morphometry; Cortical thickness; Gyrification; Pediatric HIV.

Abstract

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