title: The immunological and virological consequences of planned treatment interruptions in children with HIV infection.
abstract: OBJECTIVE
  To evaluate the immunological and viral consequences of planned treatment interruptions (PTI) in children with HIV.
  
  
  METHODS
  This was an immunological and virological sub-study of the Paediatric European Network for Treatment of AIDS (PENTA) 11 trial, which compared CD4-guided PTI of antiretroviral therapy (ART) with continuous therapy (CT) in children.
  
  
  METHODS
  HIV-1 RNA and lymphocyte subsets, including CD4 and CD8 cells, were quantified on fresh samples collected during the study; CD45RA, CD45RO and CD31 subpopulations were evaluated in some centres. For 36 (18 PTI, 18 CT) children, immunophenotyping was performed and cell-associated HIV-1 DNA analysed on stored samples to 48 weeks.
  
  
  RESULTS
  In the PTI group, CD4 cell count fell rapidly in the first 12 weeks off ART, with decreases in both naïve and memory cells. However, the proportion of CD4 cells expressing CD45RA and CD45RO remained constant in both groups. The increase in CD8 cells in the first 12 weeks off ART in the PTI group was predominantly due to increases in RO-expressing cells. PTI was associated with a rapid and sustained increase in CD4 cells expressing Ki67 and HLA-DR, and increased levels of HIV-1 DNA.
  
  
  CONCLUSIONS
  PTI in children is associated with rapid changes in CD4 and CD8 cells, likely due to increased cell turnover and immune activation. However, children off treatment may be able to maintain stable levels of naïve CD4 cells, at least in proportion to the memory cell pool, which may in part explain the observed excellent CD4 cell recovery with re-introduction of ART.
authors.affiliation: Institute of Child Health, University College London, London, United Kingdom.
authors.forename: Nigel
authors.initials: N
authors.lastname: Klein
authors.forename: Delali
authors.initials: D
authors.lastname: Sefe
authors.forename: Ilaria
authors.initials: I
authors.lastname: Mosconi
authors.forename: Marisa
authors.initials: M
authors.lastname: Zanchetta
authors.forename: Hannah
authors.initials: H
authors.lastname: Castro
authors.forename: Marianne
authors.initials: M
authors.lastname: Jacobsen
authors.forename: Hannah
authors.initials: H
authors.lastname: Jones
authors.forename: Stefania
authors.initials: S
authors.lastname: Bernardi
authors.forename: Deenan
authors.initials: D
authors.lastname: Pillay
authors.forename: Carlo
authors.initials: C
authors.lastname: Giaquinto
authors.forename: A Sarah
authors.initials: AS
authors.lastname: Walker
authors.forename: Diana M
authors.initials: DM
authors.lastname: Gibb
authors.forename: Anita
authors.initials: A
authors.lastname: De Rossi
mesh_terms: D000293:Adolescent; D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D006801:Humans; D016130:Immunophenotyping; D018655:Lymphocyte Count; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents