title: CD4 cell response to 3 doses of subcutaneous interleukin 2: meta-analysis of 3 Vanguard studies.
abstract: BACKGROUND
  In advance of a large clinical end point trial evaluating the effectiveness of subcutaneous interleukin 2 (scIL-2) for treatment of patients with human immunodeficiency virus (HIV) infection, 3 identically designed Vanguard trials were conducted in Buenos Aires, Argentina; Bangkok, Thailand; and Houston, Texas. To more precisely quantitate the effect on CD4 cell response of 3 different doses of scIL-2 that were administered twice daily for 5 days every 8 weeks, the results of these 3 trials were pooled in a meta-analysis.
  
  
  METHODS
  Two hundred eighteen HIV-1-infected subjects who were receiving antiretroviral therapy and who had a baseline CD4 cell count of > or =350 cells/mm3 were consecutively randomized to receive scIL-2 at a dose of 1.5 mIU (n=36) or a control regimen (n=36); or scIL-2 at a dose of 4.5 mIU (n=36) or a control regimen (n=36); or scIL-2 at a dose of 7.5 mIU (n=37) or a control regimen (n=37). After completion of 3 cycles of therapy, the subjects were enrolled in an extension phase (months 6-12). Subjects were encouraged to receive additional cycles of scIL-2 to maintain a CD4 cell count of more than twice the baseline count or >1000 cells/mm3.
  
  
  RESULTS
  After completion of 3 cycles of scIL-2, the mean CD4 cell count changes from baseline (calculated as changes from baseline in a scIL-2 group minus changes from baseline in its contemporaneous control group) were 67 (P=.14), 339 (P<.0001), and 605 cells/mm3 (P<.0001) for the 1.5, 4.5, and 7.5 mIU dose groups, respectively (P<.0001 for differences among dose groups). Between months 6 and 12, a total of 78%, 39%, and 32% of subjects assigned to the 1.5, 4.5, and 7.5 mIU dose groups, respectively, needed at least 1 additional cycle to achieve the CD4 cell count goal. At 12 months, the differences in the mean change in CD4 cell count from baseline between each scIL-2 dose group and its contemporaneous control group were 184, 369, and 432 cells/mm3, respectively (P=.01 for differences among dose groups).
  
  
  CONCLUSIONS
  Although CD4 cell count increases were seen in all 3 dose groups, higher scIL-2 doses resulted in greater CD4 cell count changes after 6 months, compared with control groups.
authors.affiliation: The University of Texas Health Science Center at Houston, Houston, TX 77030, USA. Roberto.C.Arduino@uth.tmc.edu
authors.forename: Roberto C
authors.initials: RC
authors.lastname: Arduino
authors.forename: Esteban C
authors.initials: EC
authors.lastname: Nannini
authors.forename: Maria
authors.initials: M
authors.lastname: Rodriguez-Barradas
authors.forename: Shannon
authors.initials: S
authors.lastname: Schrader
authors.forename: Marcelo
authors.initials: M
authors.lastname: Losso
authors.forename: Kiat
authors.initials: K
authors.lastname: Ruxrungtham
authors.forename: Maria C
authors.initials: MC
authors.lastname: Allende
authors.forename: Sean
authors.initials: S
authors.lastname: Emery
authors.forename: Lisa
authors.initials: L
authors.lastname: Fosdick
authors.forename: James
authors.initials: J
authors.lastname: Neaton
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Tavel
authors.forename: Richard T
authors.initials: RT
authors.lastname: Davey
authors.forename: H Clifford
authors.initials: HC
authors.lastname: Lane
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects*; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D007376:Interleukin-2