title: Early but limited effects of raltegravir intensification on CD4 T cell reconstitution in HIV-infected patients with an immunodiscordant response to antiretroviral therapy.
abstract: BACKGROUND
  Immune hyperactivation in immunodiscordant patients can induce residual HIV replication and limit CD4 T cell recovery. We assessed the impact of raltegravir intensification on CD4 T cell recovery and viral persistence.
  
  
  METHODS
  We performed a randomized, controlled, pilot trial. Patients with CD4 T cell counts <350 cells/mm(3) despite suppressive antiretroviral therapy were randomized (2 : 1) to intensify with raltegravir (intensified arm, n = 30) or to continue with the same regimen (control arm, n = 14) for 48 weeks. Then, the control individuals intensified their treatment for 24 weeks (delayed-intensification arm). We analysed changes in CD4 T cell counts, total and episomal HIV DNA in peripheral blood mononuclear cells and predictive factors for response.
  
  
  RESULTS
  Raltegravir intensification induced a rapid increase in CD4 T cell counts (week 12) (P = 0.007), although this was not sustained over time. Control patients maintained constant but slow increases in CD4 T cell counts (present in the pre-study period), reaching CD4 T cell counts similar to those of patients in the intensification arm at week 48. This effect was confirmed by the analysis of the delayed-intensification arm. Proviral DNA levels remained stable in both arms over time; episomal DNA forms and ultrasensitive plasma viral load were barely detected during the study. Increases in CD4 T cell counts were associated with low baseline CD95 expression in CD4 and CD8 T cells (P = 0.020).
  
  
  CONCLUSIONS
  Raltegravir intensification modestly impacts viral dynamics and induces a rapid but limited gain in CD4 T cell counts in immunodiscordant patients. Residual viral replication does not seem to be the main cause of unsatisfactory CD4 T cell recovery in these patients.
authors.affiliation: Lluita contra la SIDA foundation, Institut de Recerca en Ciències de la Salut Germans Trias i Pujol (IGTP), Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain.
authors.forename: Eugènia
authors.initials: E
authors.lastname: Negredo
authors.forename: Marta
authors.initials: M
authors.lastname: Massanella
authors.forename: Maria C
authors.initials: MC
authors.lastname: Puertas
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Buzón
authors.forename: Jordi
authors.initials: J
authors.lastname: Puig
authors.forename: Núria
authors.initials: N
authors.lastname: Pérez-Alvárez
authors.forename: Josué
authors.initials: J
authors.lastname: Pérez-Santiago
authors.forename: Anna
authors.initials: A
authors.lastname: Bonjoch
authors.forename: José
authors.initials: J
authors.lastname: Moltó
authors.forename: Antoni
authors.initials: A
authors.lastname: Jou
authors.forename: Patricia
authors.initials: P
authors.lastname: Echeverría
authors.forename: Josep M
authors.initials: JM
authors.lastname: Llibre
authors.forename: Javier
authors.initials: J
authors.lastname: Martínez-Picado
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Julià
authors.initials: J
authors.lastname: Blanco
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D001769:Blood / Q000821:virology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011760:Pyrrolidinones / Q000008:administration & dosage*; D000068898:Raltegravir Potassium; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium
keywords: discordant patients; immune recovery; integrase inhibitor; viral suppression