Systemic biological mechanisms underpin poor post-discharge growth among severely wasted children with HIV

Evans O. Mudibo (), Jasper Bogaert, Caroline Tigoi, Moses M. Ngari, Benson O. Singa, Christina L. Lancioni, Abdoulaye Hama Diallo, Emmie Mbale, Ezekiel Mupere, John Mukisa, Johnstone Thitiri, Molline Timbwa, Elisha Omer, Narshion Ngao, Robert Musyimi, Eunice Kahindi, Roseline Maïmouna Bamouni, Robert H. J. Bandsma, Paul Kelly, Andrew J. Prendergast, Christine J. McGrath, Kirkby D. Tickell, Judd L. Walson, James A. Berkley, James M. Njunge () and Gerard Bryan Gonzales ()
Additional contact information
Evans O. Mudibo: KEMRI-Wellcome Trust Research Programme
Jasper Bogaert: Ghent University
Caroline Tigoi: KEMRI-Wellcome Trust Research Programme
Moses M. Ngari: KEMRI-Wellcome Trust Research Programme
Benson O. Singa: The Childhood Acute Illness and Nutrition Network
Christina L. Lancioni: The Childhood Acute Illness and Nutrition Network
Abdoulaye Hama Diallo: University Joseph Ki-Zerbo
Emmie Mbale: Kamuzu University of Health Sciences
Ezekiel Mupere: Makerere University College of Health Sciences
John Mukisa: Department of Immunology and Department of Molecular Biology Makerere University College of Health Sciences
Johnstone Thitiri: KEMRI-Wellcome Trust Research Programme
Molline Timbwa: KEMRI-Wellcome Trust Research Programme
Elisha Omer: KEMRI-Wellcome Trust Research Programme
Narshion Ngao: KEMRI-Wellcome Trust Research Programme
Robert Musyimi: KEMRI-Wellcome Trust Research Programme
Eunice Kahindi: KEMRI-Wellcome Trust Research Programme
Roseline Maïmouna Bamouni: University Joseph Ki-Zerbo
Robert H. J. Bandsma: Hospital for Sick Children
Paul Kelly: Queen Mary University of London
Andrew J. Prendergast: Queen Mary University of London
Christine J. McGrath: The Childhood Acute Illness and Nutrition Network
Kirkby D. Tickell: The Childhood Acute Illness and Nutrition Network
Judd L. Walson: The Childhood Acute Illness and Nutrition Network
James A. Berkley: KEMRI-Wellcome Trust Research Programme
James M. Njunge: KEMRI-Wellcome Trust Research Programme
Gerard Bryan Gonzales: Wageningen University & Research

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract 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 SomaScanTM 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.

Date: 2024
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DOI: 10.1038/s41467-024-54717-w

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