title: Virologically suppressed patients with asymptomatic and symptomatic HIV-associated neurocognitive disorders do not display the same pattern of immune activation.
abstract: OBJECTIVE
  Inversion of the CD4:CD8 ratio is a marker of immune activation and age-associated disease. We measured the CD4:CD8 ratio as a marker of cognitive impairment in HIV-infected patients and explored differences according to clinical severity.
  
  
  METHODS
  Post hoc analysis of data from two prospective cohorts of HIV-infected patients randomly selected to undergo neuropsychological tests was performed. Test scores were adjusted for age, gender and education. Inclusion criteria were undetectable viral load and stable treatment for at least 6 months. Subjects with HIV-associated dementia were excluded. Patients were divided into an unimpaired group, a group with asymptomatic neurocognitive disorder (ANI) and a group with symptomatic HIV-associated neurocognitive disorder (sHAND), represented by mild neurocognitive disorder (MND). Demographic and background parameters, immune activation markers and the CD4:CD8 ratio were recorded.
  
  
  RESULTS
  Two hundred patients were included in the study. The mean age was 52 years, 78% were male, the mean CD4 count was 624 cells/μL, the mean nadir CD4 count was 240 cells/μL, 27% were hepatitis C virus (HCV)-coinfected, the mean duration of HIV infection was 16 years, and the mean time on current combination antiretroviral therapy (cART) was 2.9 years. Twenty-nine per cent of subjects had HAND (21% had ANI and 8% had MND). In multivariate analysis, a CD4:CD8 ratio < 1 was associated with a nadir CD4 count < 200 cells/μL [odds ratio (OR) 3.68] and with the presence of CD4(+) CD38(+) HLA(+) cells (OR 1.23). Multinominal logistic regression showed that, in comparison with the unimpaired group, diagnosis of sHAND was associated with a CD4:CD8 ratio < 1 (OR 10.62), longer HIV infection (OR 1.15) and longer current cART (OR 1.34), while the ANI group differed from the unimpaired group only for education level.
  
  
  CONCLUSIONS
  Aviraemic patients with sHAND did not display the same pattern of immune activation as subjects with ANI, suggesting that the underlying pathophysiological mechanisms could be different.
authors.affiliation: Department of Infectious Diseases, L'Archet Hospital, University of Nice, Nice, France.|Department of Internal Medicine, Cannes General Hospital, Cannes, France.
authors.forename: M
authors.initials: M
authors.lastname: Vassallo
authors.affiliation: Department of Infectious Diseases, L'Archet Hospital, University of Nice, Nice, France.
authors.forename: J
authors.initials: J
authors.lastname: Durant
authors.affiliation: Department of Neurology, Pasteur Hospital, University of Nice, Nice, France.
authors.forename: C
authors.initials: C
authors.lastname: Lebrun-Frenay
authors.affiliation: Department of Public Health, L'Archet Hospital, University of Nice, Nice, France.
authors.forename: R
authors.initials: R
authors.lastname: Fabre
authors.affiliation: Immunology Laboratory Unit, L'Archet Hospital, University of Nice, Nice, France.
authors.forename: M
authors.initials: M
authors.lastname: Ticchioni
authors.affiliation: Department of Infectious Diseases, L'Archet Hospital, University of Nice, Nice, France.
authors.forename: S
authors.initials: S
authors.lastname: Andersen
authors.affiliation: Department of Infectious Diseases, L'Archet Hospital, University of Nice, Nice, France.
authors.forename: F
authors.initials: F
authors.lastname: DeSalvador
authors.affiliation: Department of Infectious Diseases, L'Archet Hospital, University of Nice, Nice, France.
authors.forename: A
authors.initials: A
authors.lastname: Harvey-Langton
authors.affiliation: Department of Infectious Diseases, L'Archet Hospital, University of Nice, Nice, France.|Department of Public Health, L'Archet Hospital, University of Nice, Nice, France.
authors.forename: B
authors.initials: B
authors.lastname: Dunais
authors.affiliation: AbbVie Laboratoiries, Rungis, France.
authors.forename: I
authors.initials: I
authors.lastname: Cohen-Codar
authors.affiliation: Department of Internal Medicine, Cannes General Hospital, Cannes, France.
authors.forename: N
authors.initials: N
authors.lastname: Montagne
authors.affiliation: Department of Infectious Diseases, L'Archet Hospital, University of Nice, Nice, France.|Department of Internal Medicine, Cannes General Hospital, Cannes, France.
authors.forename: E
authors.initials: E
authors.lastname: Cua
authors.affiliation: Department of Internal Medicine, Cannes General Hospital, Cannes, France.
authors.forename: L
authors.initials: L
authors.lastname: Fredouille-Heripret
authors.affiliation: Department of Neurology, Pasteur Hospital, University of Nice, Nice, France.
authors.forename: M
authors.initials: M
authors.lastname: Laffon
authors.affiliation: Virology Laboratory Unit, L'Archet Hospital, University of Nice, Nice, France.
authors.forename: J
authors.initials: J
authors.lastname: Cottalorda
authors.affiliation: Department of Infectious Diseases, L'Archet Hospital, University of Nice, Nice, France.
authors.forename: P
authors.initials: P
authors.lastname: Dellamonica
authors.affiliation: Department of Public Health, L'Archet Hospital, University of Nice, Nice, France.
authors.forename: C
authors.initials: C
authors.lastname: Pradier
mesh_terms: D015526:AIDS Dementia Complex / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D016516:CD4-CD8 Ratio; D003072:Cognition Disorders / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D003430:Cross-Sectional Studies; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D016015:Logistic Models; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012307:Risk Factors; D019562:Viral Load
keywords: CD4:CD8 ratio; HIV-associated neurocognitive disorders; immune activation