Immune activation is associated with decreased thymic function in asymptomatic, untreated HIV-infected individuals

Abstract

Background: Reduced thymic function causes poor immunological reconstitution in human immunodeficiency virus (HIV)-positive patients on combined antiretroviral therapy (cART).The association between immune activation and thymic function in asymptomatic HIV positive treatment-naive individuals has thus far not been investigated.

Aims and objectives: To optimise a five-colour flow cytometric assay for measurement of thymic function by measuring recent thymic emigrants (RTEs) in treatment-naive HIV-infected patients and healthy controls and correlate results with levels of immune activation, CD4 counts and viral load.

Methods: Blood obtained from 53 consenting HIV-positive individuals and 32 controls recruited from HIV prevention and testing clinic in Cape Town, South Africa. RTEs were measured (CD3⁺/CD4⁺/CD45RA⁺/CD31⁺/CD62L⁺) and levels were correlated with CD4 counts of HIV-infected individuals, log viral load and levels of immune activation (CD8⁺/CD38⁺ T-cells).

Results: HIV-infected individuals had reduced frequencies of RTEs when compared to controls (p = 0.0035). Levels of immune activation were inversely correlated with thymic function(p = 0.0403), and the thymic function in HIV-infected individuals showed no significant correlation with CD4 counts (p = 0.31559) and viral load (p = 0.20628).

Conclusions: There was impaired thymic function in HIV-infected individuals, which was associated with increased levels of immune activation. The thymic dysfunction was not associated with CD4 counts and viral load. Immune activation may result in inflammatory damage to the thymus and subsequent thymic dysfunction, and CD4 counts and viral load may not necessarily reflect thymic dysfunction in HIV.