title: Elevation and persistence of CD8 T-cells in HIV infection: the Achilles heel in the ART era.
abstract: BACKGROUND
  HIV infection leads to a disturbed T-cell homeostasis, featured by a depletion of CD4 T-cells and a persistent elevation of CD8 T-cells over disease progression. Most effort of managing HIV infection has been focused on CD4 T-cell recovery, while changes in the CD8 compartment were relatively underappreciated in the past.
  
  
  METHODS
  A comprehensive literature review of publications in English language was conducted using major electronic databases. Our search was focused on factors contributing to CD8 T-cell dynamics in HIV infection and following antiretroviral therapy (ART).
  
  
  CONCLUSIONS
  Normalization of CD8 counts is seldom observed even with optimal CD4 recovery following long-term treatment. Initiation of ART in primary HIV infection leads to enhanced normalization of CD8 count compared with long-term ART initiated in chronic infection. Importantly, such CD8 elevation in treated HIV infection is associated with an increased risk of inflammatory non-AIDS-related clinical events independent of CD4 T-cell recovery. The mechanisms underlying CD8 persistence remain largely unknown, which may include bystander activation, exhaustion and immunosenescence of CD8 T-cells. The information provided herein will lead to a better understanding of factors associated with CD8 persistence and contribute to the development of strategies aiming at CD8 normalization.
  
  
  CONCLUSIONS
  Persistence of CD8 T-cell elevation in treated HIV-infected patients is associated with an increased risk of non-AIDS-related events. Now that advances in ART have led to decreased AIDS-related opportunistic diseases, more attention has been focused on reducing non-AIDS events and normalizing persistent CD8 T-cell elevation.
authors.affiliation: Chronic Viral Illness Service, McGill University Health Centre, Montreal, QC, Canada.|Research Institute of the McGill University Health Centre, Montreal, QC, Canada.|Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.affiliation: Chronic Viral Illness Service, McGill University Health Centre, Montreal, QC, Canada.|Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
authors.forename: Vikram
authors.initials: V
authors.lastname: Mehraj
authors.affiliation: Centre de recherche du Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada.|Department of Medicine, Université de Montréal, Montreal, QC, Canada.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Kaufmann
authors.affiliation: Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Taisheng
authors.initials: T
authors.lastname: Li
authors.affiliation: Chronic Viral Illness Service, McGill University Health Centre, Montreal, QC, Canada.|Research Institute of the McGill University Health Centre, Montreal, QC, Canada.|Division of Hematology, McGill University Health Centre, Montreal, QC, Canada; jean-pierre.routy@mcgill.ca.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Routy
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006801:Humans
chemical_list: D019380:Anti-HIV Agents
keywords: CD8 T-cell persistence; HIV; T-cell exhaustion; antiretroviral therapy; bystander activation