Low Proportions of CD28 CD8+ T cells Expressing CD57 Can Be Reversed by Early ART Initiation and Predict Mortality in Treated HIV Infection

SA Lee, E Sinclair, V Jain, Y Huang… - The Journal of …, 2014 - academic.oup.com
SA Lee, E Sinclair, V Jain, Y Huang, L Epling, M Van Natta, CL Meinert, JN Martin
The Journal of infectious diseases, 2014academic.oup.com
Background. Unlike cytomegalovirus (CMV) infection and aging, human immunodeficiency
virus (HIV) decreases the proportion of CD28− CD8+ T cells expressing CD57. Whether this
abnormality predicts mortality in treated HIV infection and can be reversed by early
antiretroviral therapy (ART) remains unknown. Methods. We sampled recently HIV-infected
individuals (< 6 months) and HIV-uninfected controls and compared longitudinal changes in
the proportion of CD28− CD8+ T cells expressing CD57 between those who initiated ART …
Abstract
Background.  Unlike cytomegalovirus (CMV) infection and aging, human immunodeficiency virus (HIV) decreases the proportion of CD28CD8+ T cells expressing CD57. Whether this abnormality predicts mortality in treated HIV infection and can be reversed by early antiretroviral therapy (ART) remains unknown.
Methods.  We sampled recently HIV-infected individuals (<6 months) and HIV-uninfected controls and compared longitudinal changes in the proportion of CD28CD8+ T cells expressing CD57 between those who initiated ART early (<6 months) vs later (≥2 years). We also assessed the relationship between this phenotype and mortality in a nested case-control study of ART-suppressed chronically infected individuals.
Results.  Compared to HIV-uninfected controls (n = 15), individuals who were recently infected with HIV had lower proportions of CD28CD8+ T cells expressing CD57 (P < .001), and these proportions increased during ART. The early ART group (n = 33) achieved normal levels, whereas the later ART group (n = 30) continued to have lower levels than HIV-uninfected controls (P = .02). Among 141 ART-suppressed participants in the SOCA study, those in the lowest quartile of CD28CD8+ T cells expressing CD57 had 5-fold higher odds of mortality than those in the highest quartile (95% CI, 1.6–15.9, P = .007).
Conclusions.  Abnormally low proportions of CD28CD8+ T cells expressing CD57 predict increased mortality during treated HIV infection and may be reversed with early ART initiation.
Oxford University Press