Increased monocyte and T-cell activation in treated HIV+ ugandan children: associations with gut alteration and HIV factors.
INTRODUCTION: The pathophysiology of immune activation and its mechanisms in children living with perinatally acquired HIV (PHIV) in sub-Saharan Africa has been understudied. METHODS: We enrolled 101 children living with perinatally acquired HIV (PHIV) and 96 HIV negative controls (HIV-). All participants were between 10-18 years of age with no known active infections. PHIVs were on ART with HIV-1 RNA level <=400 copies/mL. We measured plasma and cellular markers of monocyte activation, T-cell activation (expression of CD38 and HLA-DR on CD4+ and CD8+), oxidized lipids, markers of gut integrity and fungal translocation. Spearman correlations and linear regression models were used. RESULTS: Overall median (Q1; Q3) age was 13 years (11; 15) and 52% were females. Groups were similar by age, sex and BMI. Median ART duration was 10 years (8; 11). PHIVs had higher monocyte and T-cell activation; higher sCD14 (p = 0.01) and elevated frequencies of non-classical monocytes (p < 0.001 for both). Markers of systemic inflammation (hsCRP), fungal translocation (BDG), intestinal permeability (zonulin) and oxidized lipids (ox LDL) correlated with monocyte and T cell activation in PHIV (<=0.05). After adjusting for age, sex, ART duration, protease inhibitor and non-nucleoside reverse transcriptase inhibitor use, a modest association between BDG and activated CD4+ T cells was observed (beta=0.65, p < 0.01). Oxidized LDL was inversely associated with activated T cells, inflammatory and non-classical monocytes (p < 0.01). CONCLUSION: Ugandan children with perinatally acquired HIV with viral suppression have evidence of ongoing immune activation. Intestinal barrier dysfunction and fungal translocation may be involved in chronic immune dysfunction.
|Authors:||Dirajlal-Fargo S, Albar Z, Bowman E, Labbato D, Sattar A, Karungi C, Nazzinda R, Funderburg N, Kityo C, Musiime V, McComsey GA,|
|Journal:||AIDS; 2020 Feb 17 . doi:10.1097/QAD.0000000000002505|
|PubMed:||PMID: 32073452 (Go to PubMed)|