TY - JOUR
T1 - Plasma proteomics reveals markers of metabolic stress in HIV infected children with severe acute malnutrition
AU - Gonzales, Gerard Bryan
AU - Njunge, James M.
AU - Gichuki, Bonface M.
AU - Wen, Bijun
AU - Potani, Isabel
AU - Voskuijl, Wieger
AU - Bandsma, Robert H. J.
AU - Berkley, James A.
N1 - Funding Information: The original clinical trial was supported by the Thrasher Fund (Grant number: 9403), awarded to JAB. GBG is a postdoctoral fellow of the Research Foundation—Flanders (FWO). The Ghent University—VLIR-UOS Global Minds Fund supported the travel of GBG to Kenya. JAB and JMN are currently supported by the Bill & Melinda Gates Foundation within the Childhood Acute Illness and Nutrition (CHAIN) Network (Grant OPP1131320). JAB is currently supported by the MRC/DfID/Wellcome Trust Joint Global Health Trials scheme (Grant MR/ M007367/1). The funders had no role in the design, conduct, analysis, or writing of this manuscript. Publisher Copyright: © 2020, The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - HIV infection affects up to 30% of children presenting with severe acute malnutrition (SAM) in Africa and is associated with increased mortality. Children with SAM are treated similarly regardless of HIV status, although mechanisms of nutritional recovery in HIV and/or SAM are not well understood. We performed a secondary analysis of a clinical trial and plasma proteomics data among children with complicated SAM in Kenya and Malawi. Compared to children with SAM without HIV (n = 113), HIV-infected children (n = 54) had evidence (false discovery rate (FDR) corrected p < 0.05) of metabolic stress, including enriched pathways related to inflammation and lipid metabolism. Moreover, we observed reduced plasma levels of zinc-α-2-glycoprotein, butyrylcholinesterase, and increased levels of complement C2 resembling findings in metabolic syndrome, diabetes and other non-communicable diseases. HIV was also associated (FDR corrected p < 0.05) with higher plasma levels of inflammatory chemokines. Considering evidence of biomarkers of metabolic stress, it is of potential concern that our current treatment strategy for SAM regardless of HIV status involves a high-fat therapeutic diet. The results of this study suggest a need for clinical trials of therapeutic foods that meet the specific metabolic needs of children with HIV and SAM.
AB - HIV infection affects up to 30% of children presenting with severe acute malnutrition (SAM) in Africa and is associated with increased mortality. Children with SAM are treated similarly regardless of HIV status, although mechanisms of nutritional recovery in HIV and/or SAM are not well understood. We performed a secondary analysis of a clinical trial and plasma proteomics data among children with complicated SAM in Kenya and Malawi. Compared to children with SAM without HIV (n = 113), HIV-infected children (n = 54) had evidence (false discovery rate (FDR) corrected p < 0.05) of metabolic stress, including enriched pathways related to inflammation and lipid metabolism. Moreover, we observed reduced plasma levels of zinc-α-2-glycoprotein, butyrylcholinesterase, and increased levels of complement C2 resembling findings in metabolic syndrome, diabetes and other non-communicable diseases. HIV was also associated (FDR corrected p < 0.05) with higher plasma levels of inflammatory chemokines. Considering evidence of biomarkers of metabolic stress, it is of potential concern that our current treatment strategy for SAM regardless of HIV status involves a high-fat therapeutic diet. The results of this study suggest a need for clinical trials of therapeutic foods that meet the specific metabolic needs of children with HIV and SAM.
UR - http://www.scopus.com/inward/record.url?scp=85087684952&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41598-020-68143-7
DO - https://doi.org/10.1038/s41598-020-68143-7
M3 - Article
C2 - 32641735
SN - 2045-2322
VL - 10
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 11235
ER -