title: 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.
authors.affiliation: University of California San Francisco, San Francisco, California.
authors.forename: Sulggi A
authors.initials: SA
authors.lastname: Lee
authors.affiliation: University of California San Francisco, San Francisco, California.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sinclair
authors.affiliation: University of California San Francisco, San Francisco, California.
authors.forename: Vivek
authors.initials: V
authors.lastname: Jain
authors.affiliation: University of California San Francisco, San Francisco, California.
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: University of California San Francisco, San Francisco, California.
authors.forename: Lorrie
authors.initials: L
authors.lastname: Epling
authors.affiliation: Johns Hopkins University, Baltimore, Maryland.
authors.forename: Mark
authors.initials: M
authors.lastname: Van Natta
authors.affiliation: Johns Hopkins University, Baltimore, Maryland.
authors.forename: Curtis L
authors.initials: CL
authors.lastname: Meinert
authors.affiliation: University of California San Francisco, San Francisco, California.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Martin
authors.affiliation: University of California San Francisco, San Francisco, California.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: McCune
authors.affiliation: University of California San Francisco, San Francisco, California.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.affiliation: Case Western Reserve University, Cleveland, Ohio.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
authors.affiliation: University of California San Francisco, San Francisco, California.
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Hecht
authors.affiliation: University of California San Francisco, San Francisco, California.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Hunt
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology*; D018106:CD28 Antigens / Q000235:genetics / Q000378:metabolism*; D018959:CD57 Antigens / Q000235:genetics / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D006801:Humans; D018655:Lymphocyte Count; D008297:Male
chemical_list: D019380:Anti-HIV Agents; D018106:CD28 Antigens; D018959:CD57 Antigens
keywords: CD28; CD57; HIV; Immunosenescence; aging; antiretroviral therapy; immune activation; mortality