Altered methionine-sulfone levels are associated with impaired growth in HIV-exposed-uninfected children

Objective:To determine immune-metabolic dysregulation in children born to women living with HIV.Methods:Longitudinal immune-metabolomic analyses of plasma of 32 pregnant women with HIV (WHIV) and 12 uninfected women and their children up to 1.5 years of age were performed.Results:Using liquid chromatography-mass spectrometry and a multiplex bead assay, 280 metabolites (57 amino acids, 116 positive lipids, 107 signalling lipids) and 24 immune mediators (e.g. cytokines) were quantified. combinational antiretroviral therapy (cART) exposure was categorized as cART initiation preconception (long), cART initiation postconception up to 4 weeks before birth (medium) and cART initiation within 3 weeks of birth (short). Plasma metabolite profiles differed between HIV-exposed-uninfected (HEU)-children with long cART exposure compared to HIV-unexposed-children (HUU). Specifically, higher levels of methionine-sulfone, which is associated with oxidative stress, were detected in HEU-children with long cART exposure compared to HUU-children. High infant methionine-sulfone levels were reflected by high prenatal plasma levels in the mother. Increased methionine-sulfone levels in the children were associated with decreased growth, including both weight and length.Conclusion:These findings based on longitudinal data demonstrate that dysregulation of metabolite networks associated with oxidative stress in children born to WHIV is associated with restricted infant growth.