Metabolic Alterations in Mothers Living with HIV and Their HIV-Exposed, Uninfected Infants

Louise D V du Toit; Shayne Mason; Mari van Reenen; Theresa M Rossouw; Roan Louw

doi:10.3390/v16020313

Metabolic Alterations in Mothers Living with HIV and Their HIV-Exposed, Uninfected Infants

Viruses. 2024 Feb 19;16(2):313. doi: 10.3390/v16020313.

Authors

Louise D V du Toit^{1

2

3}, Shayne Mason⁴, Mari van Reenen⁴, Theresa M Rossouw^{1

2

3}, Roan Louw⁴

Affiliations

¹ Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa.
² UP Research Centre for Maternal, Fetal, Newborn and Child Health Care Strategies, University of Pretoria, Pretoria 0001, South Africa.
³ Maternal and Infant Health Care Strategies Research Unit, South African Medical Research Council, Pretoria 0001, South Africa.
⁴ Human Metabolomics, Faculty of Natural and Agricultural Sciences, North-West University, Potchefstroom 2520, South Africa.

Abstract

HIV-exposed, uninfected (HEU) children present with suboptimal growth and a greater susceptibility to infection in early life when compared to HIV-unexposed, uninfected (HUU) children. The reasons for these findings are poorly understood. We used a metabolomics approach to investigate the metabolic differences between pregnant women living with HIV (PWLWH) and their HEU infants compared to the uninfected and unexposed controls. Untargeted metabolomic profiling was performed using ¹H-NMR spectroscopy on maternal plasma at 28 weeks' gestation and infant plasma at birth, 6/10 weeks, and 6 months. PWLWH were older but, apart from a larger 28 week mid-upper-arm circumference, anthropometrically similar to the controls. At all the time points, HEU infants had a significantly reduced growth compared to HUU infants. PWLWH had lower plasma 3-hydroxybutyric acid, acetoacetic acid, and acetic acid levels. In infants at birth, threonine and myo-inositol levels were lower in the HEU group while formic acid levels were higher. At 6/10 weeks, betaine and tyrosine levels were lower in the HEU group. Finally, at six months, 3-hydroxyisobutyric acid levels were lower while glycine levels were higher in the HEU infants. The NMR analysis has provided preliminary information indicating differences between HEU and HUU infants' plasma metabolites involved in energy utilization, growth, and protection from infection.

Keywords: HEU; HIV-exposed uninfected; NMR; infant health; metabolomics; profile.

MeSH terms

Betaine
Child
Female
HIV Infections* / prevention & control
Humans
Infant
Infant, Newborn
Metabolomics
Mothers
Pregnancy

Substances

Betaine

Grants and funding

The umbrella study, of which this study forms a part, was largely funded by Collaborative Initiative for Paediatrics HIV Education and Research (CIPHER) funding from the International AIDS Society. Funding was obtained in 2017 for the protocol “Assessment of factors impacting on fetal and infant immunity and growth in HIV- and antiretroviral-exposed uninfected children” (the “Siyakhula study”); CIPHER Grant ID 2017/560-FEU.