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

Anna-Ursula Happel, Lerato Rametse, Brandon Perumaul, Christian Diener, Sean M Gibbons, Donald D Nyangahu, Kirsten A Donald, Clive Gray, Heather B Jaspan

Journal: BMC complementary medicine and therapies 2023;23(1):367

PMID: 37853370

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Abstract

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 × 10 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.

Address: Department of Pathology, University of Cape Town, Anzio Road, Observatory, Cape Town, 7925, South Africa. [email protected].; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Anzio Road, Observatory, Cape Town, 7925, South Africa. [email protected].; Department of Pathology, University of Cape Town, Anzio Road, Observatory, Cape Town, 7925, South Africa.; Institute for Systems Biology, Seattle, WA, 98109, USA.; Department of Bioengineering, University of Washington, Seattle, WA, 98195, USA.; Department of Genome Sciences, University of Washington, Seattle, WA, 98195, USA.; eScience Institute, University of Washington, Seattle, WA, 98195, USA.; Seattle Children's Research Institute, 307 Westlake Ave. N, Seattle, WA, 98109, USA.; Division of Developmental Paediatrics, Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Klipfontein Road Rondebosch, Cape Town, 7700, South Africa.; The Neuroscience Institute, University of Cape Town, Anzio Road, Observatory, Cape Town, 7925, South Africa.; Division of Molecular Biology and Human Genetics, Stellenbosch University, Francie Van Zijl Drive, Tygerberg, 7505, South Africa.; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Anzio Road, Observatory, Cape Town, 7925, South Africa.; Department of Pediatrics, University of Washington, 1959 NE Pacific St, Seattle, WA, 98195, USA.; Department of Global Health, University of Washington, 1510 San Juan Road NE, Seattle, WA, 98195, USA.

DOI: 10.1186/s12906-023-04208-0

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MeSH Terms: Female, Humans, Infant, Pregnancy, Bifidobacterium longum subspecies infantis, Dietary Supplements, HIV Infections, Randomized Controlled Trials as Topic, South Africa, Vaccines