Plasma proteomics reveals markers of metabolic stress in HIV infected children with severe acute malnutrition

Abstract

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.

Effects of Undernutrition and Predictors on the Survival Status of HIV-Positive Children after Started Antiretroviral Therapy (ART) in Northwest Ethiopia

“…In the same year, in Ethiopia, 44229 children were diagnosed with HIV and 2055 died related to AIDS [ 9 , 15 ]. Undernutrition in all its forms remains a global public health burden that accounts for 45% of all deaths for people living with HIV [ 2 , 16 ]. Children are more vulnerable to undernutrition than adults with HIV; hence, rapid viral replication and a higher rate of CD4 cell destruction are inevitable due to immature immunity [ 17 ].…”

Gut microbiota and childhood malnutrition: Understanding the link and exploring therapeutic interventions

“…It is noteworthy that non‐infectious factors, such as high‐risk genetic polymorphisms and hypermetabolic stress affected by hormonal and immune reactions, are also linked to the etiology of undernutrition through inducing tissues wasting and rapid consumption of energy reserves [ 2 , 43 ].…”

“…Nutritionally speaking, childhood malnutrition includes both under‐ and overeating, and in the clinical setting, it can present with both chronic and acute symptoms [ 1 ]. Malnutrition is the leading cause of half of all deaths in children under the age of five, the primary target group, and even in the most optimistic survival mode, it has negative physical and neurological impacts [ 2 , 3 ]. Therefore, malnourished children are vulnerable compared to their healthy peers and aberrant immune responses, mental retardation, invasion of infectious agents, mood instability, cardiac, metabolic, and orthopedic failures can potentially threaten their lives [ 4 , 5 ].…”

Inflammation: the driver of poor outcomes among children with severe acute malnutrition?

“… 85 Consistent with this, children with HIV and SAM have higher levels of inflammatory markers, including immunoglobulins, calprotectin, complement, and proteins related to the host response to infection, such as lipopolysaccharide binding protein, compared with children with SAM alone. 86 …”