Frailty, markers of immune activation and oxidative stress in HIV infected elderly

Susana Álvarez,Santiago Moreno,Fátima Brañas,Juan Carlos López-Bernaldo De Quirós,Matilde Sánchez-Conde,Mª Ángeles Muñoz-Fernández,Douglas F Nixon

doi:10.1371/journal.pone.0230339

Abstract

People living with HIV-1 experience an accelerated aging due to the persistent and chronic activation of the immune system. This phenomenon conduces to immune exhaustion and precipitate immunosenescence. In general, frailty is defined as a syndrome of physiological degeneration in the elderly. Circulating naïve and memory T cells were studied by flow cytometry in non-frail and frail HIV-1-infected groups. Thymopoiesis, cell activation, senescence and cell proliferation were analyzed by CD31, HLA-DR/CD38, CD28/CD57 and Ki-67 expression, respectively. Plasma levels of sCD14 and MDA were measured by ELISA. Frail infected individuals showed a reduced number of memory T cells, both CD4+ and CD8+ populations. Activated CD3+CD4+HLA-DR+ T cells were lower in frail individuals, and directly correlated with CD3+CD8+HLA-DR+ and CD8M cells. Senescent CD8+CD28−CD57+ cells were reduced in frail HIV-1 infected individuals and inversely correlated with CD8RTE, CD8N and CD3+CD4+HLA-DR+. Higher plasma levels of sCD14 and MDA were found in HIV-1 infected frail individuals. Our data show association among frailty, markers of immune activation and oxidative stress. Understanding the immune mechanisms underlying frailty status in HIV-1 population is of high relevance not only for the prediction of continuing longevity but also for the identification of potential strategies for the elderly.

Highlights

With the advent of antiretroviral therapy combination (ARTc), people living with HIV-1 (PLWH) are surviving to older age [1]
We matched 35 control patients by age, nadir CD4 T-cell count, current CD4+ T cells, CD4/CD8 ratio, undetectable viral load and years living with HIV-1
When the CD8M and CD8N levels were explored, we found that the frequency of CD8M and CD8N subsets were reduced in the frail group compared to the non-frail group (10.94 vs. 13.61, and 9.47 vs. 13.74, respectively), but again the differences were not significant between both groups (Fig 1c and 1d)

Summary

Introduction

With the advent of antiretroviral therapy combination (ARTc), people living with HIV-1 (PLWH) are surviving to older age [1]. HIV-1 infection and aging are associated with immune activation and inflammation [2], and even with the suppression of the viral load and a partial immune reconstitution, HIV-1+ individuals present a profound immune activation. This activation in PLWH could contribute to aging and to the development of chronic diseases. Frailty is a common clinical syndrome in the elderly. This syndrome is related to a major.

Methods

Results

Conclusion