title: Effects of interleukin-2 therapy combined with highly active antiretroviral therapy on immune restoration in HIV-1 infection: a randomized controlled trial.
abstract: BACKGROUND
  Intermittent interleukin-2 (IL-2) therapy leads to a sustained increase of CD4 T cells in HIV-1-infected patients.
  
  
  METHODS
  Symptom-free HIV-1-infected patients who were naive to all antiretroviral drugs (n = 68) and/or to protease inhibitors (n = 50) and had a CD4 cell count of 200-550 x 10(6) cells/l were randomly assigned to start lamivudine/stavudine/indinavir alone (controls) or combined from week 4 with subcutaneous IL-2 (5 x 10(6) IU twice daily for 5 days: every 4 weeks for three cycles, then every 8 weeks for seven cycles). Immunological and virological results were monitored until week 74.
  
  
  RESULTS
  CD4 T cell counts increased more in the IL-2 group than in the controls (median increases 865 and 262 x 10(6) cells/l, respectively; P < 0.0001); an 80% increase in CD4 T cells was achieving by 89% of the IL-2 group and by 47% of the controls (P < 0.0001). Decrease of plasma viral loads was similar in both groups. Compared with controls, IL-2 induced a greater increase of naive and memory CD4 T cells, lymphocyte expression of CD28 and CD25 (P < 0.0001) and natural killer cells (P < 0.001). In a logistic regression analysis, odds of being responders to recall antigens was 8.5-fold higher in IL-2 recipients (P = 0.002) than in controls. The former experienced a higher level of antibody response to tetanus vaccination at week 64 than controls (32 and 8 haemagglutinating units/ml, respectively; P = 0.01).
  
  
  CONCLUSIONS
  The combination of antiviral drugs and IL-2 induced a greater expansion and function of CD4 T cells than antiretroviral drugs alone.
authors.affiliation: Unit of Clinical Immunology, Hospital Henri Mondor, 51 avenue du Maréchal de Lattre de Tassigny, 94010 Créteil Cedex, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Levy
authors.forename: Christine
authors.initials: C
authors.lastname: Durier
authors.forename: Roman
authors.initials: R
authors.lastname: Krzysiek
authors.forename: Claire
authors.initials: C
authors.lastname: Rabian
authors.forename: Catherine
authors.initials: C
authors.lastname: Capitant
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Lascaux
authors.forename: Christophe
authors.initials: C
authors.lastname: Michon
authors.forename: Eric
authors.initials: E
authors.lastname: Oksenhendler
authors.forename: Laurence
authors.initials: L
authors.lastname: Weiss
authors.forename: Jean-Albert
authors.initials: JA
authors.lastname: Gastaut
authors.forename: Cécile
authors.initials: C
authors.lastname: Goujard
authors.forename: Christine
authors.initials: C
authors.lastname: Rouzioux
authors.forename: Jean
authors.initials: J
authors.lastname: Maral
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Delfraissy
authors.forename: Dominique
authors.initials: D
authors.lastname: Emilie
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Aboulker
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D000917:Antibody Formation; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004279:DNA, Viral / Q000032:analysis; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012367:RNA, Viral / Q000097:blood; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000276:Adjuvants, Immunologic; D004279:DNA, Viral; D007376:Interleukin-2; D012367:RNA, Viral