title: Dynamics of CD8 T-cell activation after discontinuation of HIV treatment intensification.
abstract: BACKGROUND
  Detection of episomal HIV cDNA has been associated with greater levels of CD8 and CD4 T-cell activation in HIV-1-infected highly active antiretroviral therapy (HAART)-suppressed individuals. However, HAART intensification exclusively reduced CD8 T-cell activation.
  
  
  METHODS
  We evaluated activation markers 12 weeks after raltegravir withdrawal in a previously described 48-week raltegravir intensification study. The subjects (n = 34) were subgrouped into 2-LTR(+) (n = 12) or 2-LTR(-) (n = 22) subgroups according to delectability of 2-LTR episomes during the intensification period.
  
  
  RESULTS
  The initial differences in CD8 T-cell activation between subgroups were lost after intensification. Linear mixed models revealed significant reductions in CD8 T-cell activation in both 2-LTR(-) and 2-LTR(+) subgroups, suggesting that raltegravir impacts subjects irrespective of 2-LTR detection. Remarkably, a partial rebound in CD8 activation markers after raltegravir discontinuation was observed in the 2-LTR(+) subgroup. This restored the differences between subgroups observed at study entry, particularly in terms of CD38 expression within CD8 memory T-cells. Conversely, CD4 T-cell activation remained unchanged in both subgroups during the study period, although an early and transient CD45RA(-) CD4 T-cell redistribution from tissues was apparent.
  
  
  CONCLUSIONS
  CD8 T-cell activation undergoes reversible changes during raltegravir intensification and discontinuation in patients showing detectable 2-LTR circles. The general decrease in CD8 T-cell activation and a transient CD45RA(-) CD4 T-cell redistribution in intensified individuals may reflect residual viral replication during apparently suppressive HAART.
authors: IrsiCaixa, Institut de Recerca de la SIDA, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.
authors: Marta
authors: M
authors: Massanella
authors: Anna
authors: A
authors: Esteve
authors: Maria J
authors: MJ
authors: Buzón
authors: Josep M
authors: JM
authors: Llibre
authors: Maria C
authors: MC
authors: Puertas
authors: Josep M
authors: JM
authors: Gatell
authors: Pere
authors: P
authors: Domingo
authors: Mario
authors: M
authors: Stevenson
authors: Bonaventura
authors: B
authors: Clotet
authors: Javier
authors: J
authors: Martinez-Picado
authors: Julià
authors: J
authors: Blanco
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000096:biosynthesis; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D011760:Pyrrolidinones / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D000068898:Raltegravir Potassium; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D011760:Pyrrolidinones; D012367:RNA, Viral; D000068898:Raltegravir Potassium; D051997:ADP-ribosyl Cyclase 1