Premature immunosenescence in HIV-infected patients on highly active antiretroviral therapy with low-level CD4 T cell repopulation

Abstract

Objectives

To analyse the role of thymic function and its association with cellular immunosenescence markers in patients with low-level CD4 T cell repopulation, despite complete HIV RNA replication control on highly active antiretroviral therapy (HAART).

Methods

Cellular immunosenescence markers comparing patients with CD4 T cell counts ≤250 cells/mm³ for ≥48 weeks (n = 11) and patients with a CD4 T cell count ≥500 cells/mm³ (n = 11) were investigated. Both groups were also compared with 11 healthy volunteers of similar age. Naive CD4 T cell counts, β- and δ-T cell rearrangement excision circles, recent thymic emigrants, replicative senescence marker, cell activation, and rate of apoptosis were analysed. The Mann–Whitney U-test was used to compare parameters between both low-level and high-level CD4 T cell repopulation groups, and healthy volunteers.

Results

Our results showed a lower thymic activity in patients with low-level CD4 T cell repopulation, leading to a decline in CD4 T cell production. On the other hand, a higher activation along with a higher replicative senescence of CD4 T cells contributed to a higher rate of apoptotic CD4 T cells in this group of patients.

Conclusions

We propose a model with several different related mechanisms involved in premature immune senescence in HIV-infected patients with low-level CD4 repopulation on HAART. The understanding of such different mechanisms could help find effective strategies to prevent immune decay.

CD4 T cells, HIV, activation, apoptosis, thymic function, senescence, HAART