title: Relevance of HIV-1-specific CD4+ helper T-cell responses during structured treatment interruptions in patients with CD4+ T-cell nadir above 400/mm3.
abstract: OBJECTIVE
  To analyze the dynamics of both HIV-1-specific CD4 and CD8 T-cell responses during structured treatment interruptions (STIs) in chronically HIV-1-infected (CHI) patients and to correlate them with the viral set point achieved.
  
  
  METHODS
  Forty-five early-stage CHI patients who were on highly active antiretroviral therapy (HAART) for at least 1 year and underwent STI were included. Plasma viral load (VL), peripheral blood mononuclear cell (PBMC) lymphoproliferative (LPR) response to HIV p24 protein, and HIV-1 epitope-specific interferon-gammarelease from CD8 T cells were measured over a minimum study period of 2 years.
  
  
  RESULTS
  VL set point during final STI was both significantly lower than, and positively correlated to, baseline VL (P < 0.0001: mean VL reduction 0.77 log10, and r = 0.42, P = 0.004, respectively). CD4 LPRs to p24 increased significantly (P = 0.001) between day 0 of the first STI cycle and 4th STI but decreased thereafter. VL set point during final STI was significantly and negatively correlated with LPRs to p24 at both 2nd STI and 4th STI. Nevertheless, at week 52, 12 weeks after the end of the last STI, LPRs were weak and transient in all patients and were not correlated with VL set point. Moreover, the magnitude and breadth of HIV-1-specific CD8 T-cell responses increased significantly (P < 0.0001) between day 0 and week 52. The largest increases occurred during the final STI. Even though VL reached set point by week 12 of the final STI, HIV-1-specific CD8 T-cell responses did not stabilize but rather increased until the end of the follow-up and did not correlate with plasma VL (r = 0.01, P = 0.88).
  
  
  CONCLUSIONS
  STIs do not lead to control of viral replication in CHI patients, probably due to the fact that boosted CTL responses lack strong and durable helper T-cell responses. To reset the VL set point, new approaches that effectively augment and preserve helper T-cell responses should be investigated.
authors.affiliation: Clinic Institute of Infectious Diseases and Immunology, IDIBAPS, Hospital Clínic, Faculty of Medicine, University of Barcelona, Spain. mplana@medicina.ub.es
authors.forename: Montserrat
authors.initials: M
authors.lastname: Plana
authors.forename: Felipe
authors.initials: F
authors.lastname: Garcia
authors.forename: Annette
authors.initials: A
authors.lastname: Oxenius
authors.forename: Gabriel M
authors.initials: GM
authors.lastname: Ortiz
authors.forename: Anna
authors.initials: A
authors.lastname: Lopez
authors.forename: Anna
authors.initials: A
authors.lastname: Cruceta
authors.forename: Gabriel
authors.initials: G
authors.lastname: Mestre
authors.forename: Emilio
authors.initials: E
authors.lastname: Fumero
authors.forename: Catherine
authors.initials: C
authors.lastname: Fagard
authors.forename: Maria Antonia
authors.initials: MA
authors.lastname: Sambeat
authors.forename: Ferran
authors.initials: F
authors.lastname: Segura
authors.forename: José M
authors.initials: JM
authors.lastname: Miró
authors.forename: Mireia
authors.initials: M
authors.lastname: Arnedo
authors.forename: Lucia
authors.initials: L
authors.lastname: Lopalcos
authors.forename: Tomas
authors.initials: T
authors.lastname: Pumarola
authors.forename: Bernard
authors.initials: B
authors.lastname: Hirschel
authors.forename: Rodney E
authors.initials: RE
authors.lastname: Phillips
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Nixon
authors.forename: Teresa
authors.initials: T
authors.lastname: Gallart
authors.forename: Jose M
authors.initials: JM
authors.lastname: Gatell
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage*; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004334:Drug Administration Schedule; D005805:Genes, MHC Class I; D016655:HIV Core Protein p24; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D016056:Immunodominant Epitopes; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D019380:Anti-HIV Agents; D016655:HIV Core Protein p24; D006680:HLA Antigens; D016056:Immunodominant Epitopes