Bifidobacterium infantis supplementation versus placebo in early life to improve immunity in infants exposed to HIV: a protocol for a randomized trial.

INTRODUCTION: Infants who are born from mothers with HIV (infants who are HIV exposed but uninfected; iHEU) are at higher risk of morbidity and display multiple immune alterations compared to infants who are HIV-unexposed (iHU). Easily implementable strategies to improve immunity of iHEU, and possibly subsequent clinical health outcomes, are needed. iHEU have altered gut microbiome composition and bifidobacterial depletion, and relative abundance of Bifidobacterium infantis has been associated with immune ontogeny, including humoral and cellular vaccine responses. Therefore, we will assess microbiological and immunological phenotypes and clinical outcomes in a randomized, double-blinded trial of B. infantis Rosell®-33 versus placebo given during the first month of life in South African iHEU. METHODS: This is a parallel, randomised, controlled trial. Two-hundred breastfed iHEU will be enrolled from the Khayelitsha Site B Midwife Obstetric Unit in Cape Town, South Africa and 1:1 randomised to receive 8 × 109 CFU B. infantis Rosell®-33 daily or placebo for the first 4 weeks of life, starting on day 1-3 of life. Infants will be followed over 36 weeks with extensive collection of meta-data and samples. Primary outcomes include gut microbiome composition and diversity, intestinal inflammation and microbial translocation and cellular vaccine responses. Additional outcomes include biological (e.g. gut metabolome and T cell phenotypes) and clinical (e.g. growth and morbidity) outcome measures. DISCUSSION: The results of this trial will provide evidence whether B. infantis supplementation during early life could improve health outcomes for iHEU. ETHICS AND DISSEMINATION: Approval for this study has been obtained from the ethics committees at the University of Cape Town (HREC Ref 697/2022) and Seattle Children's Research Institute (STUDY00003679). TRIAL REGISTRATION: Pan African Clinical Trials Registry Identifier: PACTR202301748714019. TRIALS: gov: NCT05923333. PROTOCOL VERSION: Version 1.8, dated 18 July 2023.