title: Early and delayed benefits of HIV-1 suppression: timeline of recovery of innate immunity effector cells.
abstract: OBJECTIVE
  The kinetics of recovery for innate immune effectors following antiretroviral therapy are unknown.
  
  
  METHODS
  Multiple sequential cryopreserved samples (viremic and ART-suppressed) from 66 patients enrolled in the Women's Interagency HIV Study or Multicenter AIDS Cohort Study cohorts (median follow-up, 700 days) were analyzed to determine natural killer, dendritic and T-cell changes by flow cytometry. Functional parameters were also measured in a subset of samples. Changes over time were analyzed by mixed-effect modeling based on a linear spline with a single knot at 270 days.
  
  
  RESULTS
  Following viral suppression, a rapid rise in CD4 and white blood cell counts and a decline in T-cell activation were confirmed. However, natural killer cell subsets increased after 270 days of therapy, with a negative effect by baseline CD4%. CD123+ plasmacytoid but not myeloid dendritic cells showed a trend to increase during the first 270 days with a positive effect of baseline CD4%; plasmacytoid dendritic cell-induced interferon-alpha production significantly increased by end of follow-up.
  
  
  CONCLUSIONS
  The kinetics of natural killer and plasmacytoid dendritic cell recovery are markedly different from those of T-cell subsets, indicative of early and delayed benefits of suppressive regimens.
authors.affiliation: The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: Livio
authors.initials: L
authors.lastname: Azzoni
authors.forename: Jihed
authors.initials: J
authors.lastname: Chehimi
authors.forename: Lan
authors.initials: L
authors.lastname: Zhou
authors.forename: Andrea S
authors.initials: AS
authors.lastname: Foulkes
authors.forename: Rayford
authors.initials: R
authors.lastname: June
authors.forename: Vernon C
authors.initials: VC
authors.lastname: Maino
authors.forename: Alan
authors.initials: A
authors.lastname: Landay
authors.forename: Charles
authors.initials: C
authors.lastname: Rinaldo
authors.forename: Lisa P
authors.initials: LP
authors.lastname: Jacobson
authors.forename: Luis J
authors.initials: LJ
authors.lastname: Montaner
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D007111:Immunity, Cellular; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013997:Time Factors
chemical_list: D019380:Anti-HIV Agents