T- cell activation and senescence phenotypes among people living with hiv-1 with advanced immunosuppression

Abstract

INTRODUCTION. T cell activation and senescence phenotype markers among HIV-1 infected patients with advanced immunosuppression are key components in the immunopathogenesis of HIV. In HIV infection, senescence is accelerated resulting in an immunosuppressed state that diminishes the ability of the immune system to contain the virus while at the same time facilitating viral replication and spread. The frequencies of activation (CD38+/HLA-DR+), exhaustion (PD1+), proliferation (Ki-67+), on central and effector memory CD4+ T cell phenotypes were measured in HIV/AIDS infected patients that were either with WHO HIV clinical stages 1 &2 or 3 &4 to determine their expression at week 0 before HAART initiation and 4 weeks after initiation of ART and an enhanced antimicrobial prophylaxis from the REALITY trial. AIM: Compared the mean frequencies of T cell activation (CD38+/HLADR+), exhaustion (PD1+), proliferation (Ki-67+), terminal differentiation (CD45RA+/CD27-), central memory (CD45RA-/CD27+) and effector memory (CD45RA-/CD27-) markers on CD4+T cells in patients with WHO Clinical stages 1&2 and 3&4. Also compared the longitudinal changes at week 0 and 4 of the activation, differentiation, proliferation and exhaustion markers regardless of the WHO stage. METHODS: This was a retrospective study where stored cells from the REALITY study that were collected at baseline (week 0) (before ART initiation) and week 4 (after ART initiation) were used. The samples were run on the MACSQUANT Miltenyi flow cytometer and data analyzed using Flowjo 10.0 to determine the frequencies of these markers, statistically used Non parametric tests for differences at week 0 and 4 (Wilcoxon test) and for differences between the stages (MannWhitney test) and a significant p value of <0.05 was considered. RESULTS: For comparison between week 0 and 4, there was a significant difference in the exhaustion marker (p=0.0008), effector memory (p=0.05), naïve cells (p=0.02) with no significant difference in the activation and proliferation markers in the WHO clinical HIV stages. There was no difference in the frequencies of activated (p=0.24) and proliferated (p=0.6) CD4+T cells between week 0 and 4 with a significant difference in the frequencies of exhausted (p=0.0008), naïve (p=0.02), effector memory (p=0.05) and differentiated (p=<0.0001) CD4+ T cells between CONCLUSION: In advanced HIV/AIDS stage frequencies of activated CD4+T cells do not change regardless of the WHO clinical stage within one month of ART initiation however, the frequency of exhausted CD4+ T cells do increase