Altered Intestinal Permeability and Fungal Translocation in Ugandan Children With Human Immunodeficiency Virus. (1st July 2019)

• Record Type: Journal Article
• Authors: Dirajlal-Fargo, Sahera; El-Kamari, Vanessa; Weiner, Lukasz; Shan, Lingpeng; Sattar, Abdus; Kulkarni, Manjusha; Funderburg, Nicholas; Nazzinda, Rashidah; Karungi, Christine; Kityo, Cissy; Musiime, Victor; McComsey, Grace A
• Is Part Of: Clinical infectious diseases. Volume 70:Number 11(2020)
• Page Start: 2413
• Page End: 2422
• Publication Date: 2019-07-01
• Subjects: children with HIV -- HIV-exposed uninfected infants -- gut integrity -- inflammation -- translocation; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciz561
• Languages: English
• ISSNs: 1058-4838

Abstract

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.