BackgroundChildren who are HIV-exposed uninfected (HEU), i.e., born to mothers living with HIV despite not acquiring HIV infection themselves, have increased morbidity and mortality. Data suggests that the breastmilk profile, and more specifically human milk oligosaccharide (HMO) composition, differ by maternal HIV status and may partly help explain this increased risk. We are currently conducting an HMO-based synbiotic randomized trial in breastfed children HEU, the MIGH-T MO study (ClinicalTrials.govIdentifier:NCT05282485), to assess the impact on health outcomes of children HEU. Here, we report our experience from a study of the feasibility and acceptability of a powder-based intervention given to breastfeeding children, conducted prior to the initiation of MIGH-T MO.Methods10 mothers living with HIV and their breastfeeding children HEU accessing care at Tygerberg Hospital, in Cape Town, South Africa were enrolled. A powder-based product, potato maltodextrin, was mixed with expressed breast milk and administered to the infants daily for 4 weeks. Data on feasibility, acceptability, adherence, and health outcomes were assessed at the enrollment visit and at the 4 week visit, along with weekly telephone calls.Results10 mother-infant pairs were enrolled in this study, with infant age ranging from 6–20 months of age. Among the mothers who met the eligibility criteria, all of them enrolled into the study suggesting high acceptability. While there was some Ioss-to-follow-up after the first visit, among the mothers who remained, there were no major feasibility concerns related to study procedures, product administration, adherence, tolerance, and health outcome assessment.ConclusionOur pilot study demonstrated that a powder-based intervention for breastfeeding children HEU in South Africa is acceptable and feasible. This suggests potential feasibility and acceptability for other larger studies, including our ongoing MIGH-T MO study, that use similar powder-based interventions such as probiotics, prebiotics, or synbiotics, in breastfed infants from similar settings.