title: Course and Clinical Significance of CD8+ T-Cell Counts in a Large Cohort of HIV-Infected Individuals.
abstract: OBJECTIVE
  To examine trajectories of CD8(+) T-cell counts before and after combination antiretroviral therapy (cART) in human immunodeficiency virus (HIV)-infected individuals and associations with mortality.
  
  
  METHODS
  CD8(+) T-cell counts were measured in 3882 HIV-infected individuals who received care in Copenhagen during 1995-2012. Reference values were obtained from 1230 persons from the background population. Mortality rate ratios were estimated by Poisson regression.
  
  
  RESULTS
  CD8(+) T-cell counts were elevated during untreated HIV infection and remained elevated through 10 years of cART. A slight drop of 130 cells/µL (interquartile range, -160 to 410 cells/μL) in the median CD8(+) T-cell count was observed after cART initiation. CD8(+) T-cell counts stabilized at approximately 900 cells/µL (95th percentile of the background population, 835 cells/µL). Markedly elevated CD8(+) T-cell counts at cART initiation were associated with a poor increase in the CD4(+) T-cell count (relative risk, 2.22; 95% confidence interval [CI], 1.42-3.48). Individuals with a CD8(+) T-cell count of <500 cells/µL 1 year after cART initiation had an increased mortality rate (mortality rate ratio, 1.73; 95% CI, 1.29-2.32) and a higher proportion of deaths attributable to AIDS-related conditions, compared with individuals with CD8(+) T-cell counts of ≥500 cells/µL. After receiving cART for 10 years, a CD8(+) T-cell count of >1500 cells/µL was associated with increased non-AIDS-related mortality (mortality rate ratio, 1.82; 95% CI, 1.09-3.22), compared with a CD4(+) T-cell count of 500-1500 cells/µL.
  
  
  CONCLUSIONS
  CD8(+) T-cell counts are elevated during HIV infection and do not normalize despite long-term cART. Low CD8(+) T-cell counts are associated with increased AIDS-related mortality. Marked elevations in CD8(+) T-cell counts after long-term cART are associated with increased non-AIDS-related mortality.
authors.affiliation: Department of Infectious Diseases.
authors.forename: Marie
authors.initials: M
authors.lastname: Helleberg
authors.affiliation: Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre Hospital, Denmark.
authors.forename: Gitte
authors.initials: G
authors.lastname: Kronborg
authors.affiliation: Department of Clinical Immunology.
authors.forename: Henrik
authors.initials: H
authors.lastname: Ullum
authors.affiliation: The Tissue Type Laboratory, Copenhagen University Hospital, Rigshospitalet, Copenhagen.
authors.forename: Lars P
authors.initials: LP
authors.lastname: Ryder
authors.affiliation: Department of Infectious Diseases.
authors.forename: Niels
authors.initials: N
authors.lastname: Obel
authors.affiliation: Department of Infectious Diseases.
authors.forename: Jan
authors.initials: J
authors.lastname: Gerstoft
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003718:Denmark / Q000453:epidemiology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000276:immunology* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D044966:Anti-Retroviral Agents
keywords: CD8; HIV; immune activation; immunological recovery; mortality