title: Inferiority of IL-2 alone versus IL-2 with HAART in maintaining CD4 T cell counts during HAART interruption: a randomized controlled trial.
abstract: OBJECTIVE
  To evaluate whether interleukin (IL)-2 in patients with chronic HIV infection can maintain CD4 T cell counts during 6 months of HAART interruption.
  
  
  METHODS
  Prospective, randomized, controlled, open-label phase II noninferiority trial comparing IL-2 with HAART interruption or continuous HAART.
  
  
  METHODS
  Forty-one IL-2-experienced (three or more prior cycles) HIV-1-infected adults with CD4 cell count at least 500 cells/microl were randomized in the ratio 2: 1 to interrupted (I = 27) or continuous (C = 14) HAART for 6 months following an initial IL-2 cycle. Subsequent IL-2 cycles were triggered by CD4 T cell counts less than 90% of baseline. Immune, metabolic, and quality of life indices were compared (Mann-Whitney and Fisher's exact tests), defining noninferiority as a percentage difference (C- I) in treatment success (CD4 T cells > or =90% of baseline at 6 months) with a 95% confidence interval (CI) lower limit greater than -20%.
  
  
  RESULTS
  Demographic and immune parameters were similar between the groups at baseline. Median CD4 T cell count, HIV viral load, and treatment success differed significantly at 6 months (I: 866 cells/microl, 39,389 copies/ml, 48.1%; C: 1246 cells/microl, <50 copies/ml, 92.3%; P < or = 0.001). Group I was inferior to C (% difference = -44.2%; 95% CI: -64.2%, -11.2%; P = 0.013). Minor statistically significant differences in HgbA1c and energy level occurred at 6 months (I > C). Following HAART interruption, single cases of acute retroviral syndrome, secondary syphilis, non-Hodgkin's lymphoma, and Kaposi's sarcoma recurrence were observed.
  
  
  CONCLUSIONS
  IL-2 alone was inferior to IL-2 with HAART in maintaining baseline CD4 T cell counts. HAART interruption had a small impact on metabolic parameters and quality of life.
authors.affiliation: National Institute of Allergy & Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20982, USA.
authors.forename: Brian O
authors.initials: BO
authors.lastname: Porter
authors.forename: Kara B
authors.initials: KB
authors.lastname: Anthony
authors.forename: Jean
authors.initials: J
authors.lastname: Shen
authors.forename: Barbara
authors.initials: B
authors.lastname: Hahn
authors.forename: Chris E
authors.initials: CE
authors.lastname: Keh
authors.forename: Frank
authors.initials: F
authors.lastname: Maldarelli
authors.forename: William C
authors.initials: WC
authors.lastname: Blackwelder
authors.forename: Henry Clifford
authors.initials: HC
authors.lastname: Lane
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Kovacs
authors.forename: Richard T
authors.initials: RT
authors.lastname: Davey
authors.forename: Irini
authors.initials: I
authors.lastname: Sereti
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011788:Quality of Life; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D007376:Interleukin-2