Early structural brain development in infants exposed to HIV and antiretroviral therapy in utero in a South African birth cohort.

Journal: Journal of the International AIDS Society

Volume: 25

Issue: 1

Year of Publication: 2022

Affiliated Institutions:  Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa. The Neuroscience Institute, University of Cape Town, Cape Town, South Africa. Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK. MRC International Statistics & Epidemiology Group, London School of Hygiene & Tropical Medicine, London, UK. MRC Clinical Trials Unit, University College London, London, UK. Departments of Neurology, Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, California, USA.

Abstract summary 

There is a growing population of children who are HIV-exposed and uninfected (HEU) with the successful expansion of antiretroviral therapy (ART) use in pregnancy. Children who are HEU are at risk of delayed neurodevelopment; however, there is limited research on early brain growth and maturation. We aimed to investigate the effects of in utero exposure to HIV/ART on brain structure of infants who are HEU compared to HIV-unexposed (HU).Magnetic resonance imaging using a T2-weighted sequence was undertaken in a subgroup of infants aged 2-6 weeks enrolled in the Drakenstein Child Health Study birth cohort, South Africa, between 2012 and 2015. Mother-child pairs received antenatal and postnatal HIV testing and ART per local guidelines. We compared subcortical and total grey matter volumes between HEU and HU groups using multivariable linear regression adjusting for infant age, sex, intracranial volume and socio-economic variables. We further assessed associations between brain volumes with maternal CD4 cell count and ART exposure.One hundred forty-six infants (40 HEU; 106 HU) with high-resolution images were included in this analysis (mean age 3 weeks; 50.7% male). All infants who were HEU were exposed to ART (88% maternal triple ART). Infants who were HEU had smaller caudate volumes bilaterally (5.4% reduction, p < 0.05) compared to HU infants. There were no group differences in other subcortical volumes (all p > 0.2). Total grey matter volume was also reduced in infants who were HEU (2.1% reduction, p < 0.05). Exploratory analyses showed that low maternal CD4 cell count (<350 cells/mm ) was associated with decreased infant grey matter volumes. There was no relationship between timing of ART exposure and grey matter volumes.Lower caudate and total grey matter volumes were found in infants who were HEU compared to HU in the first weeks of life, and maternal immunosuppression was associated with reduced volumes. These findings suggest that antenatal HIV exposure may impact early structural brain development and improved antenatal HIV management may have the potential to optimize neurodevelopmental outcomes of children who are HEU.

Authors & Co-authors:  Wedderburn Catherine J CJ Groenewold Nynke A NA Roos Annerine A Yeung Shunmay S Fouche Jean-Paul JP Rehman Andrea M AM Gibb Diana M DM Narr Katherine L KL Zar Heather J HJ Stein Dan J DJ Donald Kirsten A KA

Study Outcome 

Source Link: Visit source

Statistics
Citations :  Slogrove AL, Powis KM, Johnson LF, Stover J, Mahy M. Estimates of the global population of children who are HIV‐exposed and uninfected, 2000–18: a modelling study. Lancet Glob Health. 2020;8(1):e67–75.
Authors :  11
Identifiers
Doi : e25863
SSN : 1758-2652
Study Population
Male,Female
Mesh Terms
Birth Cohort
Other Terms
HIV exposure;antiretroviral therapy;brain structure;child development;magnetic resonance imaging;newborn infant
Study Design
Exploratory Study,Cross Sectional Study
Study Approach
Country of Study
South Africa
Publication Country
Switzerland