T cell Activation does not drive CD4 decline in longitudinally followed HIV-infected Elite Controllers

Thirty four EC were studied. The slope of CD4 count change was available for 25 of these subjects. We assessed immune activation by measuring the percent of CD38+HLA-DR+CD8+ T cells in the EC group and comparing it with that in 24 treatment-na？ve HIV disease progressors and 13 HIV uninfected healthy controls.Compared to HIV uninfected subjects, EC had higher percentages of CD38+HLA-DR+CD8+ T cells (p < 0.001) that was lower than that observed in progressors (p < 0.01). Fifteen of 25 EC had a slope of CD4 count change that was not significantly different from 0 while 3 had a positive and 7 a negative CD4 count slope. Immune activation did not distinguish EC subsets with stable/increasing versus declining CD4 counts.Elevated immune activation in ECs is not associated with a faster rate of CD4 declineUntreated HIV infection is usually characterized by viral replication and chronic generalized immune activation, which is thought to be an important driver of CD4 decline in HIV infection [1-6]. Markers of immune activation such as CD38 can be found on a high proportion of the CD8+ T cells in HIV infected individuals. CD38, an ectoenzyme involved in transmembrane signaling and cell adhesion, is ubiquitous in its distribution among cells of the immune system and is a marker of both activation and differentiation [7]. HLA-DR is a human major histocompatability complex (MHC) class II antigen that is expressed on macrophages, monocytes, B cells and on activated T and NK cells. The co-expression of CD38 and HLA-DR on CD8+ T cells has been used to detect immune activation in HIV infected individuals with low-level viremia and to distinguish populations that spontaneously control VL from those successfully treated with anti-retroviral drugs [8,9].While stimulation of the immune system by HIV likely induces anti-viral immunity that plays a role in suppression of viral replication, chronic immune activation of non HIV-specific T cells reflects rapid cell turnover due to increased e