HIV-Infected Subjects With Poor CD4 T-Cell Recovery Despite Effective Therapy Express High Levels of OX40 and α4β7 on CD4 T-Cells Prior Therapy Initiation

Description

Background HIV-infected subjects with suboptimal CD4 restoration despite suppressive combined antiretroviral treatment (cART) (immunodiscordant subjects) have been classically characterized after a variable period of time under cART. Recently, we have reported that an increased frequency of proliferating CD4 T-cells in these subjects is already present before the cART onset. The potential contribution of peripheral compensatory homeostatic proliferation (HP) is yet unknown. We aimed to analyze the expression of HP-related cellular markers on CD4 T-cells of immunodiscordant subjects before cART. Go to: Methods We analyzed the expression of OX40 and α4β7 on peripheral CD4 T-cells from immunodiscordant and control subjects (n = 21 each group) before cART initiation, and also on available follow-up samples (after 24 month of suppressive cART). Additionally, we tested the expression of these markers in an in vitro system for the study of human HP processes. Go to: Results Immunodiscordant subjects showed increased levels of OX40 and α4β7 on CD4 T-cells before cART initiation. While the cART tended to reduce these levels, immunodiscordant subjects still maintained comparatively higher levels of OX40 and α4β7 after 24 months under suppressive cART. These HP-related markers were upregulated in vitro during the human HP, especially during the fast HP. Go to: Conclusion Our results are compatible with exacerbated HP processes in immunodiscordant subjects, already before the cART onset.

Abstract

Fondo de Investigación Sanitaria FIS PI14/01693 PI13/0796 PI16/0503

Abstract

Fondos Europeos para el Desarrollo Regional (FEDER) CTS2593

Abstract

Junta de Andalucía. Consejería de Economía, Innovación, Ciencia y Empleo CTS2593

Abstract

AGAUR 2017SGR948

Abstract

GILEAD GLD14/293

Abstract

The Spanish AIDS Research Network of Excellence RD12/0017/0029 RD16/0025/0019 RD16/0025/0006

Abstract

Junta de Andalucía. Consejería de Salud y Bienestar Social C-0013-2017

Additional details