title: Low CD4/CD8 Ratio Is Associated with Non AIDS-Defining Cancers in Patients on Antiretroviral Therapy: ANRS CO8 (Aproco/Copilote) Prospective Cohort Study.
abstract: OBJECTIVE
  To study the association between CD4/CD8 ratio and morbidity in HIV-infected patients on antiretroviral therapy (ART).
  
  
  METHODS
  The APROCO/COPILOTE cohort enrolled patients initiating a protease inhibitor-containing ART in 1997-1999. The association between occurrence of first non AIDS-defining severe events (NADE) and time-dependent measures of immune restoration was assessed by 4 Cox models with different definitions of restoration, CD4+ cell counts (CD4), CD4/CD8 ratio, both CD4 and CD4/CD8 ratio, or a composite variable (CD4< 500/mm3, CD4 > 500/mm3 and CD4/CD8 ratio < 1, CD4 > 500/mm3 and CD4/CD8 ratio > 1). Models adjusted on baseline characteristics and time-dependent viral load were compared using Akaike Information Criterion.
  
  
  RESULTS
  We included 1227 patients. Median duration of follow-up was 9.2 years (IQR: 4.2-11.4). Median CD4 was 530/mm3 at 9 years. Median CD4/CD8 ratio was 0.3 (IQR: 0.2-0.5) at baseline and 0.6 (IQR: 0.4-0.9) after 9 years. Incidence of first NADE was 7.4/100 person-years, the most common being bacterial infections (21%), cardiovascular events (14%) and cancers (10%). For both bacterial infections and cardiovascular events, the CD4/CD8 ratio did not add predictive information to the CD4 cell count. However, low CD4/CD8 ratio was the best predictor of non-AIDS cancers (adjusted HR = 2.13 for CD4/CD8 < 0.5; 95% CI = 1.32-3.44).
  
  
  CONCLUSIONS
  CD4/CD8 ratio remains < 1 in most HIV-infected patients despite long-term CD4+ cell counts restoration on ART. A CD4/CD8 ratio < 0.5 could identify patients who require a more intensive strategy of cancer prevention or screening.
authors.affiliation: UMI 233 IRD/Université de Montpellier, Montpellier, France.
authors.forename: Mariam Noelie
authors.initials: MN
authors.lastname: Hema
authors.affiliation: Hospices civils de Lyon, Université Claude Bernard, Lyon, France.
authors.forename: Tristan
authors.initials: T
authors.lastname: Ferry
authors.affiliation: CHU de Bordeaux, Bordeaux, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Dupon
authors.affiliation: INSERM, UMR 1027, Toulouse, Université de Toulouse III, CHU de Toulouse, Toulouse, France.
authors.forename: Lise
authors.initials: L
authors.lastname: Cuzin
authors.affiliation: CHU de Caen, EA 4655 Risques microbiens, Université de Caen, Caen, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: Verdon
authors.affiliation: INSERM U897, Université de Bordeaux, Bordeaux, France.
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Thiébaut
authors.affiliation: INSERM UMR_S 912 (SESSTIM), Université Aix-Marseille, ORS PACA, Marseille, France.
authors.forename: Camelia
authors.initials: C
authors.lastname: Protopopescu
authors.affiliation: CMIT, 46 Rue Henri Huchard, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Leport
authors.affiliation: Infectious Diseases Department, University Hospital, Nantes, France.
authors.forename: François
authors.initials: F
authors.lastname: Raffi
authors.affiliation: UMI 233 IRD/Université de Montpellier, Montpellier, France.|CHU de Montpellier, Montpellier, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Le Moing
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D001424:Bacterial Infections / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D005260:Female; D006678:HIV / Q000187:drug effects / Q000254:growth & development; D015658:HIV Infections / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology; D009369:Neoplasms / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy / Q000517:prevention & control*; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D019562:Viral Load
chemical_list: D015415:Biomarkers; D017320:HIV Protease Inhibitors