PLoS ONE (Jan 2021)

Activation and gut-homing of peripheral T cells in HIV immunologic non-responders despite long term viral suppression.

  • Rodney K Rousseau,
  • Leah Szadkowski,
  • Colin M Kovacs,
  • Michael F Saikali,
  • Rabea Nadeem,
  • Fat Malazogu,
  • Sanja Huibner,
  • Carolyn L Cummins,
  • Rupert Kaul,
  • Sharon L Walmsley

DOI
https://doi.org/10.1371/journal.pone.0254149
Journal volume & issue
Vol. 16, no. 7
p. e0254149

Abstract

Read online

ObjectiveSerious non-AIDS disease events (SNAE) are experienced disproportionately by immunologic non-responders (INRs), HIV-infected individuals who do not restore CD4 T cells in blood despite effective viral suppression. We aimed to characterize the inflammatory biomarker profile of the INR phenotype.MethodsBlinded cross-sectional cohort study comparing markers of immune activation and gut homing between INR and non-INR individuals. HIV-positive participants had HIV RNA suppression on antiretroviral therapy and were categorized as either INR (N = 36) or Clinical Responders ("CR"; CD4>350/mm3; N = 47). 18 HIV-negative comparator individuals were included. Cellular markers were assessed by flow cytometry, with soluble markers assessed by ELISA and LC/MS-MS. Multivariable linear regression models estimated the association between INR phenotype and markers, adjusting for age, sex, duration of ART, and recent infection/vaccination.ResultsINR participants demonstrated a reduced CD4/CD8 ratio (pConclusionsPeripheral CD4 non-recovery during long-term treated HIV infection is characterized by elevated CD8 activation and CD4 gut homing. Gut-focused interventions may be warranted in the INR context, and CD8 activation may serve as a surrogate endpoint for clinical interventions.