Malnutrition in HIV-Infected Children Is an Indicator of Severe Disease with an Impaired Response to Antiretroviral Therapy

Abstract

This observational study aimed to describe immunopathogenesis and treatment outcomes in children with and without severe acute malnutrition (SAM) and HIV-infection. We studied markers of microbial translocation (16sDNA), intestinal damage (iFABP), monocyte activation (sCD14), T-cell activation (CD38, HLA-DR) and immune exhaustion (PD1) in 32 HIV-infected children with and 41 HIV-infected children without SAM prior to initiation of antiretroviral therapy (ART) and cross-sectionally compared these children to 15 HIV-uninfected children with and 19 HIV-uninfected children without SAM. We then prospectively measured these markers and correlated them to treatment outcomes in the HIV-infected children at 48 weeks following initiation of ART. Plasma levels of 16sDNA, iFABP and sCD14 were measured by quantitative real time PCR, ELISA and Luminex, respectively. T cell phenotype markers were measured by flow cytometry. Multiple regression analysis was performed using generalized linear models (GLMs) and the least absolute shrinkage and selection operator (LASSO) approach for variable selection. Microbial translocation, T cell activation and exhaustion were increased in HIV-uninfected children with SAM compared to HIV-uninfected children without SAM. In HIV-infected children microbial translocation, immune activation, and exhaustion was strongly increased but did not differ by SAM-status. SAM was associated with increased mortality rates early after ART initiation. Malnutrition, age, microbial translocation, monocyte, and CD8 T cell activation were independently associated with decreased rates of CD4% immune recovery after 48 weeks of ART. SAM is associated with increased microbial translocation, immune activation, and immune exhaustion in HIV-uninfected children and with worse prognosis and impaired immune recovery in HIV-infected children on ART.

Growth in the first 5 years after antiretroviral therapy initiation among HIV‐infected children in the IeDEA West African Pediatric Cohort

“…We studied growth using four anthropometric indicators, defined by the WHO child growth standards [26,27], and expressed in Z-scores: Weight-for-age (WAZ, available for children aged 10 years or less); Height-for-age (HAZ, available for all children); Weight-for-Height (WHZ, for children aged 5 years or less) and BMI-forage (BAZ, for children aged [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. The last two anthropometric indicators were combined.…”

“…Moreover, HIVinfected children are especially affected by malnutrition, which contributes to impair their immune system and increases the risk of opportunistic infections [9,10]. Severe acute malnutrition among HIV-infected children starting ART is associated with a higher mortality risk [11][12][13], a higher risk of hospitalization [14] and an impaired response to ART [13].…”

Machine learning-selected variables associated with CD4 T cell recovery under antiretroviral therapy in very advanced HIV infection

“…A linear regression was done using the 20 variables with the greatest LASSO coefficients (top 20 contributing to the model), as in previous studies [17,18], with the purpose of assessing statistical significance, thus providing a simple output that is easy to interpret. The linear model used all samples at once (N = 67), while LASSO performed N iterations using N-1 different variable sets (N-1 = 66).…”

Perfil Epidemiológico Do Hiv Em Um Pequeno Município Potiguar / Brasil, Entre 2015 E 2018

“…A identificação precoce de crianças expostas ao HIV ou infectada verticalmente é de suma importância para indicar o início do tratamento com antirretrovirais e ações profiláticas para infecções oportunistas, além de outras manifestações clínicas 7,26,27 .…”