title: Protection versus pathology in aviremic and high viral load HIV-2 infection-the pivotal role of immune activation and T-cell kinetics.
abstract: BACKGROUND
  Many human immunodeficiency virus (HIV)-2-infected individuals remain aviremic and behave as long-term non-progressors but some progress to AIDS. We hypothesized that immune activation and T-cell turnover would be critical determinants of non-progressor/progressor status.
  
  
  METHODS
  We studied 37 subjects in The Gambia, West Africa: 10 HIV-negative controls, 10 HIV-2-infected subjects with low viral loads (HIV-2-LV), 7 HIV-2-infected subjects with high viral loads (HIV-2-HV), and 10 with HIV-1 infection. We measured in vivo T-cell turnover using deuterium-glucose labeling, and correlated results with T-cell phenotype (by flow cytometry) and T-cell receptor excision circle (TREC) abundance.
  
  
  RESULTS
  Immune activation (HLA-DR/CD38 coexpression) differed between groups with a significant trend: controls <HIV-2-LV <HIV-1 <HIV-2-HV (P < .01 for all cell types). A similar trend was observed in the pattern of in vivo turnover of memory CD4(+) and CD8(+) T-cells and TREC depletion in naive CD4(+) T-cells, although naive T-cell turnover was relatively unaffected by either infection. T-cell turnover, immune activation, and progressor status were closely associated.
  
  
  CONCLUSIONS
  HIV-2 non-progressors have low rates of T-cell turnover (both CD4(+) and CD8(+)) and minimal immune activation; high viral load HIV-2 progressors had high values, similar to or exceeding those in HIV-1 infection.
authors.affiliation: Infection and Immunity Research Institute, St George's, University of London, United Kingdom.
authors.forename: Andrea
authors.initials: A
authors.lastname: Hegedus
authors.affiliation: Medical Research Council (UK), The Gambia, West Africa.
authors.forename: Samuel
authors.initials: S
authors.lastname: Nyamweya
authors.affiliation: Infection and Immunity Research Institute, St George's, University of London, United Kingdom.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Translational Medicine Group, Cranfield Health, Cranfield University.
authors.forename: Sheila
authors.initials: S
authors.lastname: Govind
authors.affiliation: Translational Medicine Group, Cranfield Health, Cranfield University.
authors.forename: Richard
authors.initials: R
authors.lastname: Aspinall
authors.affiliation: School of Biological Sciences, Royal Holloway University of London, United Kingdom.
authors.forename: Alla
authors.initials: A
authors.lastname: Mashanova
authors.affiliation: School of Biological Sciences, Royal Holloway University of London, United Kingdom.
authors.forename: Vincent A A
authors.initials: VA
authors.lastname: Jansen
authors.affiliation: Medical Research Council (UK), The Gambia, West Africa.
authors.forename: Hilton
authors.initials: H
authors.lastname: Whittle
authors.affiliation: Medical Research Council (UK), The Gambia, West Africa.
authors.forename: Assan
authors.initials: A
authors.lastname: Jaye
authors.affiliation: Medical Research Council (UK), The Gambia, West Africa.
authors.forename: Katie L
authors.initials: KL
authors.lastname: Flanagan
authors.affiliation: Infection and Immunity Research Institute, St George's, University of London, United Kingdom.
authors.forename: Derek C
authors.initials: DC
authors.lastname: Macallan
mesh_terms: D000328:Adult; D005260:Female; D005714:Gambia; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D020276:HIV Long-Term Survivors; D015498:HIV-2 / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D019562:Viral Load; D055815:Young Adult
keywords: CD4; CD8; HIV pathogenesis; HIV-1; HIV-2; T-cell; immune activation; immune memory