title: CD4:CD8 ratio as a frontier marker for clinical outcome, immune dysfunction and viral reservoir size in virologically suppressed HIV-positive patients.
abstract: BACKGROUND
  Absolute CD4 T cell count and plasma viral load have been established as predictors of HIV disease progression, and CD4 T cell count is used as an indicator for initiation of antiretroviral therapy. Following long-term therapy, patients generally present with significant CD4 T cell recovery contrasting with persistently elevated CD8 T cell counts, which leads to a partial restoration of CD4:CD8 ratio. This review focuses on the relevance of the CD4:CD8 ratio on clinical outcomes, immune dysfunction and HIV reservoir size in long-term treated patients.
  
  
  METHODS
  We conducted a comprehensive literature review of publications in English language using major electronic databases. Our search was focused on factors contributing to CD4:CD8 T cell ratio and clinical outcome in adult HIV-positive patients in the context of treated infection.
  
  
  CONCLUSIONS
  Low CD4:CD8 ratio has been linked to ageing and acts as a predictor of mortality in the general population. This ratio may represent the combined effects of inflammation and immunological changes called "inflammaging." Although the mechanisms underlying partial correction of the CD4:CD8 ratio and persistently elevated CD8 T cell count in long-term treated patients remain poorly understood, it has been recently indicated that patients with optimal CD4 T cell recovery and low CD4:CD8 ratio still harbour increased immune activation, an immune senescent phenotype and have a higher risk of non-AIDS morbidity and mortality. This review reconsiders CD4:CD8 ratio in the light of advances in the understanding of immune dysfunction and examines its pathophysiological features and implications on clinical outcome and HIV reservoir size in long-term treated HIV-positive adults.
  
  
  CONCLUSIONS
  The CD4:CD8 ratio can contribute to the immunological evaluation of treated patients in a long-term follow-up and may be applied for monitoring both immune dysfunction and viral reservoir size in immune-based clinical trials.
authors.affiliation: Chronic Viral Illnesses Service, McGill University Health Centre, Montreal, Quebec, Canada.|Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.|Division of Infectious Diseases, Peking Union Medical College Hospital, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.affiliation: Chronic Viral Illnesses Service, McGill University Health Centre, Montreal, Quebec, Canada.|Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Vikram
authors.initials: V
authors.lastname: Mehraj
authors.affiliation: Chronic Viral Illnesses Service, McGill University Health Centre, Montreal, Quebec, Canada.|Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Kishanda
authors.initials: K
authors.lastname: Vyboh
authors.affiliation: Chronic Viral Illnesses Service, McGill University Health Centre, Montreal, Quebec, Canada.|Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.|Division of Infectious Diseases, Peking Union Medical College Hospital, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.affiliation: Division of Infectious Diseases, Peking Union Medical College Hospital, Beijing, China.
authors.forename: Taisheng
authors.initials: T
authors.lastname: Li
authors.affiliation: Chronic Viral Illnesses Service, McGill University Health Centre, Montreal, Quebec, Canada.|Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.|Division of Hematology, McGill University Health Centre, Montreal, Quebec, Canada; jean-pierre.routy@mcgill.ca.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Routy
mesh_terms: D000328:Adult; D015415:Biomarkers; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018450:Disease Progression; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D006801:Humans; D019562:Viral Load
chemical_list: D015415:Biomarkers
keywords: CD4:CD8 ratio; HIV infection; immune dysfunction; inflammation; viral reservoir