title: Predictors of CD4:CD8 ratio normalization and its effect on health outcomes in the era of combination antiretroviral therapy.
abstract: BACKGROUND
  HIV leads to CD4:CD8 ratio inversion as immune dysregulation progresses. We examined the predictors of CD4:CD8 normalization after combination antiretroviral therapy (cART) and determined whether normalization is associated with reduced progression to AIDS-defining illnesses (ADI) and death.
  
  
  METHODS
  A Canadian cohort of HIV-positive adults with CD4:CD8<1.2 prior to starting cART from 2000-2010 were analyzed. Predictors of (1) reaching a CD4:CD8 ≥ 1.2 on two separate follow-up visits >30 days apart, and (2) ADI and death from all causes were assessed using adjusted proportional hazards models.
  
  
  RESULTS
  4206 patients were studied for a median of 2.77 years and 306 (7.2%) normalized their CD4:CD8 ratio. Factors associated with achieving a normal CD4:CD8 ratio were: baseline CD4+ T-cells >350 cells/mm(3), baseline CD8+ T-cells <500 cells/mm(3), time-updated HIV RNA suppression, and not reporting sex with other men as a risk factor. There were 213 ADIs and 214 deaths in 13476 person-years of follow-up. Achieving a normal CD4:CD8 ratio was not associated with time to ADI/death.
  
  
  CONCLUSIONS
  In our study, few individuals normalized their CD4:CD8 ratios within the first few years of initiating modern cART. This large study showed no additional short-term predictive value of the CD4:CD8 ratio for clinical outcomes after accounting for other risk factors including age and HIV RNA.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: Victor
authors.initials: V
authors.lastname: Leung
authors.forename: Jennifer
authors.initials: J
authors.lastname: Gillis
authors.forename: Janet
authors.initials: J
authors.lastname: Raboud
authors.forename: Curtis
authors.initials: C
authors.lastname: Cooper
authors.forename: Robert S
authors.initials: RS
authors.lastname: Hogg
authors.forename: Mona R
authors.initials: MR
authors.lastname: Loutfy
authors.forename: Nima
authors.initials: N
authors.lastname: Machouf
authors.forename: Julio S G
authors.initials: JS
authors.lastname: Montaner
authors.forename: Sean B
authors.initials: SB
authors.lastname: Rourke
authors.forename: Chris
authors.initials: C
authors.lastname: Tsoukas
authors.forename: Marina B
authors.initials: MB
authors.lastname: Klein
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000276:immunology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D018791:CD4 Lymphocyte Count / Q000379:methods; D016516:CD4-CD8 Ratio / Q000379:methods; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D002170:Canada; D018450:Disease Progression; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006679:HIV Seropositivity / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D019562:Viral Load / Q000187:drug effects / Q000276:immunology
chemical_list: D019380:Anti-HIV Agents