Increased monocyte and T-cell activation in treated HIV+ Ugandan children: associations with gut alteration and HIV factors

AIDS. 2020 Jun 1;34(7):1009-1018. doi: 10.1097/QAD.0000000000002505.

Abstract

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 PHIV and 96 HIV-negative controls (HIV-). All participants were between 10 and 18 years of age with no known active infections. PHIVs were on ART with HIV-1 RNA level 400 copies/ml or less. 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 girls. 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 nonclassical 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 nonnucleoside reverse transcriptase inhibitor use, a modest association between BDG and activated CD4 T cells was observed (β=0.65, P < 0.01). Oxidized LDL was inversely associated with activated T cells, inflammatory and nonclassical 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Anti-HIV Agents / therapeutic use*
  • Antibodies, Fungal / blood*
  • Child
  • Female
  • Gastrointestinal Microbiome*
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV Infections / microbiology*
  • Humans
  • Lymphocyte Activation*
  • Monocytes / immunology*
  • T-Lymphocytes
  • Uganda

Substances

  • Anti-HIV Agents
  • Antibodies, Fungal