Metabolic Brain Disease

, Volume 33, Issue 2, pp 523–535 | Cite as

Altered brain morphometry in 7-year old HIV-infected children on early ART

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


Even with the increased roll out of combination antiretroviral therapy (cART), paediatric HIV infection is associated with neurodevelopmental delays and neurocognitive deficits that may be accompanied by alterations in brain structure. Few neuroimaging studies have been done in children initiating ART before 2 years of age, and even fewer in children within the critical stage of brain development between 5 and 11 years. We hypothesized that early ART would limit HIV-related brain morphometric deficits at age 7. Study participants were 7-year old HIV-infected (HIV+) children from the Children with HIV Early Antiretroviral Therapy (CHER) trial whose viral loads were supressed at a young age, and age-matched uninfected controls. We used structural magnetic resonance imaging (MRI) and FreeSurfer ( software to investigate effects of HIV and age at ART initiation on cortical thickness, gyrification and regional brain volumes. HIV+ children showed reduced gyrification compared to controls in bilateral medial parietal regions, as well as reduced volumes of the right putamen, left hippocampus, and global white and gray matter and thicker cortex in small lateral occipital region. Earlier ART initiation was associated with lower gyrification and thicker cortex in medial frontal regions. Although early ART appears to preserve cortical thickness and volumes of certain brain structures, HIV infection is nevertheless associated with reduced gyrification in the parietal cortex, and lower putamen and hippocampus volumes. Our results indicate that in early childhood gyrification is more sensitive than cortical thickness to timing of ART initiation. Future work will clarify the implications of these morphometric effects for neuropsychological function.


Gyrification Morphometry Cher Neurodevelopment Cortical thickness Paediatric HIV 



Support for this study was provided by National Research Foundation (NRF) / Department of Science and Technology (DST) South African Research Chairs Initiative. US National Institute of Allergy and Infectious Diseases (NIAID) through the Comprehensive International Program of Research on AIDS (CIPRA) network, Grant U19 AI53217. National Institutes of Health (NIH) grants R01HD071664 and R21MH096559. NRF grant CPR20110614000019421, and the Medical Research Council (MRC). The Departments of Health of the Western Cape and Gauteng, South Africa and ViiV Healthcare/GlaxoSmithKline plc provided additional support for the CHER. Postgraduate Funding Office (PFO), University of Cape Town, South Africa.

Compliance with ethical standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national Human Research Ethics Committees (HREC) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  • Emmanuel C. Nwosu
    • 1
  • Frances C. Robertson
    • 1
  • Martha J. Holmes
    • 1
  • Mark F. Cotton
    • 2
  • Els Dobbels
    • 2
  • Francesca Little
    • 3
  • Barbara Laughton
    • 2
  • Andre van der Kouwe
    • 4
    • 5
  • Ernesta M. Meintjes
    • 1
  1. 1.MRC/UCT Medical Imaging Research Unit, Division of Biomedical Engineering, Department of Human Biology, Faculty of Health Sciences, University of Cape TownCape TownSouth Africa
  2. 2.Family Clinical Research Unit, Department of Paediatrics & Child Health, Tygerberg Children’s Hospital and Faculty of Health SciencesStellenbosch UniversityCape TownSouth Africa
  3. 3.Department of Statistical Sciences, Faculty of SciencesUniversity of Cape TownCape TownSouth Africa
  4. 4.A.A. Martinos Centre for Biomedical Imaging, Department of RadiologyMassachusetts General HospitalCharlestownUSA
  5. 5.Department of RadiologyHarvard Medical SchoolBostonUSA

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