Altered Intestinal Permeability and Fungal Translocation in Ugandan Children With Human Immunodeficiency Virus

Abstract

Background Children with perinatally acquired human immunodeficiency virus (HIV; PHIVs) face a lifelong cumulative exposure to HIV and antiretroviral therapy (ART). The relationship between gut integrity, microbial translocation, and inflammation in PHIV is poorly understood. Methods This is a cross-sectional study in 57 PHIVs, 59 HIV-exposed but uninfected children, and 56 HIV-unexposed and -uninfected children aged 2–10 years old in Uganda. PHIVs were on stable ART with HIV-1 RNA <400 copies/mL. We measured markers of systemic inflammation, monocyte activation, and gut integrity. Kruskal-Wallis tests were used to compare markers by group and the Spearman correlation was used to assess correlations between biomarkers. Results The mean age of all participants was 7 years and 55% were girls. Among PHIVs, the mean CD4 % was 34%, 93% had a viral load ≤20 copies/mL, and 79% were on a nonnucleoside reverse transcriptase inhibitor regimen. Soluble cluster of differentiation 14 (sCD14), beta-D-glucan (BDG), and zonulin were higher in the PHIV group (P ≤ .01). Intestinal fatty acid binding protein (I-FABP) and lipopolysaccharide binding protein (LBP) did not differ between groups (P > .05). Among PHIVs who were breastfed, levels of sCD163 and interleukin 6 (IL6) were higher than levels in PHIV who were not breastfed (P < .05). Additionally, in PHIVs with a history of breastfeeding, sCD14, BDG, LBP, zonulin, and I-FABP correlated with several markers of systemic inflammation, including high-sensitivity C-reactive protein, IL6, d-dimer, and systemic tumor necrosis factor receptors I and II (P ≤ .05). Conclusions Despite viral suppression, PHIVs have evidence of altered gut permeability and fungal translocation. Intestinal damage and the resultant bacterial and fungal translocations in PHIVs may play a role in the persistent inflammation that leads to many end-organ diseases in adults. Despite viral suppression, children with perinatally acquired human immunodeficiency virus (HIV) in Uganda have evidence of alterations in intestinal permeability and fungal translocation, compared to HIV-exposed but uninfected and HIV-unexposed children, which may play a role in HIV-associated chronic inflammation.

Impact of Early Versus Late Antiretroviral Treatment Initiation on Naive T Lymphocytes in HIV-1-Infected Children and Adolescents – The-ANRS-EP59-CLEAC Study

“…Higher CD4T N and CD8T N levels were found to be associated with lower iFABP levels, but only in adolescents. No difference in iFABP levels was observed between HIV-1-infected and uninfected infants ( 38 – 40 ), by contrast to what has been observed in adults ( 41 ). Thus, the data reported here and in other pediatric studies indicate that gut permeability and its impact on the immune system vary with age.…”

Daily variations of gut microbial translocation markers in ART-treated HIV-infected people

“…Translocation of bacterial and fungal products is driven by epithelial gut damage and depletion of intestinal CD4-T cells and contributes to immune activation in HIV [35,50]. Clinical studies commonly use circulating I-FABP to evaluate gut damage as a measure of enterocyte cell lysis.…”

Biological Aging and Immune Senescence in Children with Perinatally Acquired HIV

“…PAMPs and DAMPs activate the immune system by binding to the extra-or intracellular domain of Toll-like receptors (TLRs), which are involved in the host inflammatory response, initiating a complex-signal transduction cascade which, via the NF-κB pathway [131], ultimately leads to increased transcription of proinflammatory cytokines (such as IL-6, IL-10, and interferon-α) that may play a role in establishing a protumorigenic inflammatory environment [66]. Several studies [132][133][134] have suggested that, despite viral suppression, children with perinatally acquired HIV have higher levels of inflammation, immune activation, and alterations in intestinal permeability, compared to HEU and HUU children. Notably, immune activation is higher in viremic than aviremic children, but microbial translocation may occur regardless of viremia and T cell activation.…”