Effects of HIV Infection on the Metabolic and Hormonal Status of Children with Severe Acute Malnutrition

Abstract

BackgroundHIV infection occurs in 30% of children with severe acute malnutrition in sub-Saharan Africa. Effects of HIV on the pathophysiology and recovery from malnutrition are poorly understood.MethodsWe conducted a prospective cohort study of 75 severely malnourished Ugandan children. HIV status/CD4 counts were assessed at baseline; auxologic data and blood samples were obtained at admission and after 14 days of inpatient treatment. We utilized metabolomic profiling to characterize effects of HIV infection on metabolic status and subsequent responses to nutritional therapy.FindingsAt admission, patients (mean age 16.3 mo) had growth failure (mean W/H z-score −4.27 in non-edematous patients) that improved with formula feeding (mean increase 1.00). 24% (18/75) were HIV-infected. Nine children died within the first 14 days of hospitalization; mortality was higher for HIV-infected patients (33% v. 5%, OR = 8.83). HIV-infected and HIV-negative children presented with elevated NEFA, ketones, and even-numbered acylcarnitines and reductions in albumin and amino acids. Leptin, adiponectin, insulin, and IGF-1 levels were low while growth hormone, cortisol, and ghrelin levels were high. At baseline, HIV-infected patients had higher triglycerides, ketones, and even-chain acylcarnitines and lower leptin and adiponectin levels than HIV-negative patients. Leptin levels rose in all patients following nutritional intervention, but adiponectin levels remained depressed in HIV-infected children. Baseline hypoleptinemia and hypoadiponectinemia were associated with increased mortality.ConclusionsOur findings suggest a critical interplay between HIV infection and adipose tissue storage and function in the adaptation to malnutrition. Hypoleptinemia and hypoadiponectinemia may contribute to high mortality rates among malnourished, HIV-infected children.

Plasma Metabolomics Biosignature According to HIV Stage of Infection, Pace of Disease Progression, Viremia Level and Immunological Response to Treatment

“…Lipid alterations in HIV-infected individuals receiving protease inhibitors based antiretroviral treatment determined using untargeted metabolomic profiling of plasma, has been previously linked to markers of inflammation, microbial translocation, and hepatic function, suggesting that dysregulated innate immune activation and hepatic dysfunction are occurring among HIV antiretrovirally-treated individuals[11]. Furthermore, metabolomic profile in HIV-infected children shows hypoleptinemia and hypoadiponectinemia and is the activation of critical adipose tissue storage and function in the adaptation to malnutrition[30]. Also, alterations in the Cerebrospinal fluid metabolome among HIV antiretrovirally-treated individuals harboring HIV-associated neurocognitive disorders reveal that persistent inflammation, glial responses, glutamate neurotoxicity, and altered brain waste disposal are associated with cognitive alteration[31].…”

Environmental Enteric Dysfunction and Growth Failure/Stunting in Global Child Health

“…33,34 Inflammation of the small intestine in EED is associated with high C-reactive protein levels and may be accompanied by release of cytokines that reduce appetite and food intake 35 and impede production and action of chondrocyte growth factors. Recent studies 36,37 found that stunted, malnourished Ugandan infants and children (age 6 months-5 years) had high levels of interleukin 6 (IL-6), which blocks growth hormone induction of insulin-like growth factor 1 (IGF-1) production and inhibits IGF action at the growth plate. 38,39 Likewise, IL-6 levels were elevated soon after delivery in a subset of Zimbabwean infants with LBW.…”

Population pharmacokinetics of abacavir and lamivudine in severely malnourished human immunodeficiency virus‐infected children in relation to treatment outcomes

“…Malnutrition is often the presenting clinical feature on initial human immunodeficiency virus (HIV) diagnosis in sub‐Saharan African children and is a significant risk factor for mortality . The causes of malnutrition in this setting are multifactorial including delays in HIV diagnosis and ART initiation with resultant increased energy expenditure and basal metabolic rate together with higher rates of opportunistic infections, diarrhoea, malabsorption, food insecurity and poverty …”

“…3 The causes of malnutrition in this setting are multifactorial including delays in HIV diagnosis and ART initiation with resultant increased energy expenditure and basal metabolic rate together with higher rates of opportunistic infections, diarrhoea, malabsorption, food insecurity and poverty. 4,5 Severely malnourished HIV-infected children experience impaired immunological and virological responses and higher mortality 6,7 compared to their nonmalnourished counterparts despite nutritional rehabilitation and ART. 8,9 Altered pharmacokinetics (PK) of antiretroviral medications in malnourished children may be an important contributor to these poorer outcomes.…”