title: Immune restoration in HIV-positive, antiretroviral-naive patients after 1 year of zidovudine/lamivudine plus nelfinavir or nevirapine.
abstract: OBJECTIVE
  To evaluate the immunological response in HIV-1-infected, antiretroviral-naive patients receiving highly active antiretroviral therapy regimen of two nucleosides plus a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor.
  
  
  METHODS
  Of 142 patients included in a randomized, open, multicentre trial comparing zidovudine/lamivudine plus nelfinavir (NFV) or nevirapine (NVP), 36 patients (16 NFV, 20 NVP) were enrolled in an immunological substudy. Mean baseline CD4 T-cell counts was 360/mm3 (range: 11-679) and mean baseline plasma viral load >50000 copies/ml (range: 2240-1468210). Viral load (VL), T-cell subsets and T-cell functions were analysed at baseline and after 1 year of treatment.
  
  
  RESULTS
  After 12 months of follow-up, plasma viral load was reduced similarly in both groups, with 78% (NFV) and 83% (NVP) of patients achieving a VL <200 copies/ml. A significant increase in CD4 T cells was observed in both groups (mean: +182 cells, P=0.001). Both regimens were similarly effective in reducing activated T cells (CD38 and DR). A significant increase of both CD4 and CD8 CD28 T cells occurred in both arms of treatment. Patients of both regimens showed a significant decrease of activated memory (CD45RA-CD45RO+) CD8 T cells and a clear increase of naive (CD45RA+CD45RO-) CD8 T cells. Peripheral blood mononuclear cell proliferative responses to polyclonal stimuli (CD3 and CD3 +CD28) as well as to ubiquitous cytomegalovirus antigen increased significantly in both groups after 12 months of follow-up. Nevertheless, neither at baseline nor after 1 year of treatment, these patients showed any significant T-cell responsiveness to HIV-1 recombinant proteins gp160 or p24.
  
  
  CONCLUSIONS
  Our data indicate that immune restoration achieved after 1 year of therapy with either NFV or NVP was similar. This reinforces the role of NVP-containing regimens as a valid option for initiating antiretroviral therapy. Nevertheless, additional therapeutic approaches should be envisaged to restore HIV-1-specific T-cell responses.
authors.affiliation: Institut Clinic d'Infeccions i Immunologia, Immunology, Infectious Diseases and Microbiology Units, Institut de Investigació Biomèdica Agusti Pi i Suñer, Hospital Clinic, University of Barcelona, Barcelona, Spain. mplana@medicina.ub.es
authors.forename: Montserrat
authors.initials: M
authors.lastname: Plana
authors.forename: Elena
authors.initials: E
authors.lastname: Ferrer
authors.forename: Catalina
authors.initials: C
authors.lastname: Martínez
authors.forename: Daniel
authors.initials: D
authors.lastname: Podzamczer
authors.forename: Felipe
authors.initials: F
authors.lastname: García
authors.forename: María J
authors.initials: MJ
authors.lastname: Maleno
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Barceló
authors.forename: Ana
authors.initials: A
authors.lastname: García
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Barberá
authors.forename: Montserrat
authors.initials: M
authors.lastname: Lacarcel
authors.forename: José M
authors.initials: JM
authors.lastname: Miró
authors.forename: Teresa
authors.initials: T
authors.lastname: Gallart
authors.forename: José M
authors.initials: JM
authors.lastname: Gatell
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006679:HIV Seropositivity / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D019888:Nelfinavir / Q000008:administration & dosage / Q000627:therapeutic use*; D019829:Nevirapine / Q000008:administration & dosage / Q000627:therapeutic use*; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D015215:Zidovudine / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D019829:Nevirapine; D019888:Nelfinavir