title: Raltegravir intensification shows differing effects on CD8 and CD4 T cells in HIV-infected HAART-suppressed individuals with poor CD4 T-cell recovery.
abstract: BACKGROUND
  Immunodiscordant HIV-infected patients show viral suppression during antiretroviral therapy but fail to recover CD4 T cells. Immunodiscordance is characterized by partial CD4 T-cell immunodeficiency and increased inflammation, activation and immunosenescence in both CD4 and CD8 T cells.
  
  
  METHODS
  A randomized, controlled, 48-week intensification study to assess the effect of raltegravir on immunological parameters in immunodiscordant patients (CD4 cell counts <350 cells/μl; viral load <50 copies/ml for >2 years). Patients were randomized (2 : 1) to intensify therapy with raltegravir (intensified arm, n = 30) or continue with the same therapy (control arm, n = 14).
  
  
  RESULTS
  Both groups showed similar immunological baseline characteristics. CD4 T-cell counts increased faster in the intensified arm (P = 0.01, week 12). However, no differences between groups were observed at week 48. Additionally, no changes in thymic output (CD45RA(+)CD31(+) cells), activation (HLA-DR(+)CD95(+) cells) or ex-vivo cell death were observed in CD4 T cells at any time point intergroups or intragroups. Conversely, intensified arm showed significant decreases in the expression of the CD8 T-cell activation marker CD38 at weeks 24-48, which were more evident in memory cells. Despite this, the levels of HLA-DR expression in CD8 T cells and plasma soluble CD14 remained stable in both arms overtime.
  
  
  CONCLUSIONS
  Long-term (48-week) raltegravir intensification failed to counterbalance CD4 T-cell deficiency and its associated features: hyperactivation and death of CD4 T cells. However, raltegravir induced a specific reduction of CD38 expression in CD8 T cells, suggesting a beneficial effect on CD8 T-cell hyperactivation, which has been linked with HIV-associated comorbidities.
authors.affiliation: AIDS Research Institute, IrsiCaixa-HIVACAT, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Barcelona, Catalonia, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Massanella
authors.forename: Eugènia
authors.initials: E
authors.lastname: Negredo
authors.forename: Jordi
authors.initials: J
authors.lastname: Puig
authors.forename: Maria C
authors.initials: MC
authors.lastname: Puertas
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Buzón
authors.forename: Núria
authors.initials: N
authors.lastname: Pérez-Álvarez
authors.forename: Jorge
authors.initials: J
authors.lastname: Carrillo
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Javier
authors.initials: J
authors.lastname: Martínez-Picado
authors.forename: Julià
authors.initials: J
authors.lastname: Blanco
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D015774:Ganciclovir / Q000031:analogs & derivatives / Q000494:pharmacology; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D006886:Hydroxychloroquine / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000494:pharmacology*; D000068898:Raltegravir Potassium; D000077562:Valganciclovir; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D006886:Hydroxychloroquine; D000077562:Valganciclovir; D015774:Ganciclovir