Systemic biological mechanisms underpin poor post-discharge growth among severely wasted children with HIV
In sub-Saharan Africa, children with severe malnutrition (SM) and HIV have substantially worse outcomes than children with SM alone, facing higher mortality risk and impaired nutritional recovery post-hospitalisation. Biological mechanisms underpinning this risk remain incompletely understood. This case-control study nested within the CHAIN cohort in Kenya, Uganda, Malawi, and Burkina Faso examined effect of HIV on six months post-discharge growth among children with SM and those at risk of malnutrition, assessed proteomic signatures associated with HIV in these children, and investigated how these systemic processes impact post-discharge growth in children with SM. Using SomaScan<sup>TM</sup> assay, 7335 human plasma proteins were quantified. Linear mixed models identified HIV-associated biological processes and their associations with post-discharge growth. Using structural equation modelling, we examined directed paths explaining how HIV influences post-discharge growth. Here, we show that at baseline, HIV is associated with lower anthropometry. Additionally, HIV is associated with protein profiles indicating increased complement activation and decreased insulin-like growth factor signalling and bone mineralisation. HIV indirectly affects post-discharge growth by influencing baseline anthropometry and modulating proteins involved in bone mineralisation and humoral immune responses. These findings suggest specific biological pathways linking HIV to poor growth, offering insights for targeted interventions in this vulnerable population.
Authors
- Johnstone Thitiri (ORCID: https://orcid.org/0000-0002-5901-6651)
- Elisha Omer
- Robert Musyimi (ORCID: https://orcid.org/0000-0001-9810-8367)
- John Mukisa (ORCID: https://orcid.org/0000-0002-9208-0313)
- Christine J. McGrath (ORCID: https://orcid.org/0000-0003-3396-0350)
- Robert Bandsma (ORCID: https://orcid.org/0000-0001-6358-4750)
- Paul Kelly (ORCID: https://orcid.org/0000-0003-0844-6448)
- Christina Lancioni (ORCID: https://orcid.org/0000-0002-0821-1211)
- Molline Timbwa (ORCID: https://orcid.org/0000-0002-1747-7943)
- James Alexander Berkley (ORCID: https://orcid.org/0000-0002-1236-849X)
- Roseline Maïmouna Bamouni (ORCID: https://orcid.org/0009-0009-2374-1059)
- Caroline Tigoi (ORCID: https://orcid.org/0000-0003-2750-7533)
- Andrew J. Prendergast (ORCID: https://orcid.org/0000-0001-7904-7992)
- Judd L. Walson (ORCID: https://orcid.org/0000-0003-4836-720X)
- Jasper Bogaert (ORCID: https://orcid.org/0000-0003-0904-8409)
- James M. Njunge (ORCID: https://orcid.org/0000-0002-8524-9133)
- Ezekiel Mupere (ORCID: https://orcid.org/0000-0002-8746-9009)
- Abdoulaye Hama Diallo (ORCID: https://orcid.org/0009-0008-2926-2860)
- Emmie Mbale (ORCID: https://orcid.org/0000-0001-7134-2858)
- Moses M. Ngari (ORCID: https://orcid.org/0000-0001-7149-5491)
- Narshion Ngao (ORCID: https://orcid.org/0000-0002-0144-9577)
- Kirkby D. Tickell (ORCID: https://orcid.org/0000-0002-4108-1236)
- Benson O. Singa (ORCID: https://orcid.org/0000-0002-6605-324X)
- Gerard Bryan Gonzales (ORCID: https://orcid.org/0000-0001-6614-3520)
- Evans O. Mudibo (ORCID: https://orcid.org/0000-0002-7980-9034)
- Eunice Kahindi
Institutions
- Université Joseph Ki-Zerbo (BF)
- Johns Hopkins University (US)
- Oregon Health & Science University (US)
- Queen Mary University of London (GB)
- University of Toronto (CA)
- University of Washington (US)
- Kamuzu Central Hospital (MW)
- Hospital for Sick Children (CA)
- Kenya Medical Research Institute (KE)
- Ghent University (BE)
- University of Oxford (GB)
- Tropical Gastroenterology & Nutrition group (ZM)
- Zvitambo Institute for Maternal and Child Health Research (ZW)
- The Childhood Acute Illness and Nutrition Network (KE)
- Centre Muraz (BF)
- Kamuzu University of Health Sciences (MW)
- Makerere University (UG)
- Wellcome Trust (GB)
- Wageningen University & Research (NL)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-11-27
- DOI
- https://doi.org/10.1038/s41467-024-54717-w
- Citations
- 5
- Primary Topic
- Child Nutrition and Water Access
- Type
- article
- Field-Weighted Citation Impact
- 1.55
Funders
- Bill and Melinda Gates Foundation
- Wellcome
- University of Washington
- Johns Hopkins University
- Queen Mary University of London
- Wellcome Trust
- National Institute for Health and Care Research
- University of Oxford
- Department for International Development
- University of Toronto
- Universiteit Gent
- Hospital for Sick Children
- Johns Hopkins Bloomberg School of Public Health
- Medical Research Council
- Wageningen University and Research
- Faculty of Medicine and Health, University of Sydney