Low proportions of CD28- CD8+ T cells expressing CD57 can be reversed by early ART initiation and predict mortality in treated HIV infection

Abstract

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 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 CD28(-)CD8(+) 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 CD28(-)CD8(+) 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 CD28(-)CD8(+) T cells expressing CD57 predict increased mortality during treated HIV infection and may be reversed with early ART initiation.

Keywords: CD28; CD57; HIV; Immunosenescence; aging; antiretroviral therapy; immune activation; mortality.

Figure 1.

Impact of early vs later initiation of ART on CD57 expression in recently HIV-infected individuals. Study design of acutely infected HIV-positive individuals and HIV-uninfected controls (A). The proportion of CD28⁻CD8⁺ T cells expressing CD57 was compared between HIV-uninfected individuals (purple) and HIV-infected individuals initiating ART “early,” <6 months of infection (red), or “later,” ≥2 years after initial infection (blue), at acute HIV diagnosis and after 1 year of ART (B). Changes in the proportion of CD28⁻CD8⁺ T cells expressing CD57 among recently HIV-infected individuals initiating ART early (C) and later (D) were also assessed over time. Individual participant trajectories shown with red lines. Linear mixed model estimated mean changes shown in thick black lines. Abbreviations: ART, antiretroviral therapy; HIV, human immunodeficiency virus.