Potential of Prebiotic Galacto-oligosaccharides in Improving Efficacy and Safety of Oral Iron Supplementation in HIV-infected Children

Overview

The objectives of this randomized controlled trial in virally suppressed HIV-positive children with anemia and/or depleted iron stores are to determine the effect of prebiotic galacto-oligosaccharides (GOS) as adjunct treatment to 12 weeks of oral iron supplementation on: 1. iron status measured by conventional iron status biomarkers, 2. fractional absorption of iron (fraction of total body iron per day, measured as Kabs, the slope of 57Fe isotopic dilution) and mean total amount of iron absorbed each day (mg Fe/day, calculated as Kabs x mean total body iron), 3. systemic and gut inflammation, as well as gut mucosal integrity, 4. gut microbiome composition, and 5. adverse effects and gastrointestinal side-effects.

Iron deficiency anemia (IDA) in childhood can impair growth and cognition, as well as reduce school performance. Furthermore, anemia frequently complicates pediatric HIV infection and predicts disease progression and mortality. However, there is no international consensus on the treatment of ID and IDA in HIV-infected children, because of concerns around the efficacy and safety of oral iron supplements. Recent studies have suggested that oral iron supplements may increase gut inflammation in African children. This could be particularly detrimental in HIV-infected children, who may have gut immune activation, enteropathy and adverse shifts in the gut microbiome. Previous stable iron isotope studies from the ETH Laboratory of Human Nutrition showed that the consumption of prebiotic galacto-oligosaccharides (GOS) together with supplemental doses of iron can increase iron absorption. In Kenyan infants, we further showed that the addition of GOS to an iron-containing micronutrient powder mitigated the adverse effects of iron on the gut microbiome. Thus, we hypothesize that providing GOS as adjunct treatment to oral iron supplementation will improve efficacy (iron absorption and iron status), reduce systemic and gut inflammation, improve mucosal integrity, and mitigated iron-induced alterations in the gut microbiome, adverse events and gastrointestinal side-effects in virally suppressed HIV-infected children.