title: Randomized, controlled phase II trial of subcutaneous interleukin-2 in combination with highly active antiretroviral therapy (HAART) in HIV patients.
abstract: OBJECTIVE
  To determine the immunological, virological and clinical effects of subcutaneous IL-2 in 44 HIV-patients in conjunction with pre-existing tri-therapy (zidovudine, 3TC, saquinavir).
  
  
  METHODS
  Partially randomized, controlled, prospective trial.
  
  
  METHODS
  Single center study at tertiary care center.
  
  
  METHODS
  Sixty four patients (CD4 count 200-500 x 10(6)/l).
  
  
  METHODS
  Fourty four patients were randomized to receive 5-day cycles of IL-2 (9 Mio IU/d) every 6 weeks (Group A) or whenever the CD4 cell count dropped below the 1.25-fold of baseline (Group B), whereas 20 control patients received the same HAART without IL-2.
  
  
  METHODS
  The optimal individual treatment interval and the immunological and virological effects of subcutaneously administered IL-2 were analysed. Importantly, the level of cellular in vivo immunity and the frequency of dermatological marker diseases and infectious complications were assessed.
  
  
  RESULTS
  IL-2 was well tolerated although fever, influenza-like symptoms and indurated injection sites were commonly encountered. After 1 year of IL-2, there was a median increase of more than 100 x 10(6)/l CD4 cells in both IL-2 groups in contrast to the controls (P < 0.01, 0.01 and not significant). The median HIV load did not increase either in plasma or in lymph nodes. Lymphocyte activation decreased as assessed by MHC class II (P < 0.001), CD25 (P < 0.001) and CD38 expression (P < 0.005). Although delayed type hypersensitivity against common recall antigens increased in both IL-2 groups, it did not reach statistical significance. However, it is of note, that in 7 of 11 (63.6%) patients delayed type hypersensitivity against recombinant HIV antigens improved significantly. Whereas there was no opportunistic infection in either IL-2 group, three cases of Kaposi's sarcoma occurred in the controls. Dermatological indicator diseases (thrush, condyloma, herpes simplex) were found to occur more frequently in the control group.
  
  
  CONCLUSIONS
  Subcutaneous IL-2 in addition to HAART was safe and led to sustained qualitative and quantitative immunological improvements in the majority of patients. Individualisation of therapy intervals further improved the efficacy and tolerance of IL-2.
authors.affiliation: Department of Dermatology and Venerology, University of Essen, Germany.
authors.forename: U R
authors.initials: UR
authors.lastname: Hengge
authors.forename: M
authors.initials: M
authors.lastname: Goos
authors.forename: S
authors.initials: S
authors.lastname: Esser
authors.forename: V
authors.initials: V
authors.lastname: Exner
authors.forename: H
authors.initials: H
authors.lastname: Dötterer
authors.forename: H
authors.initials: H
authors.lastname: Wiehler
authors.forename: C
authors.initials: C
authors.lastname: Borchard
authors.forename: K
authors.initials: K
authors.lastname: Müller
authors.forename: A
authors.initials: A
authors.lastname: Beckmann
authors.forename: M T
authors.initials: MT
authors.lastname: Eppner
authors.forename: A
authors.initials: A
authors.lastname: Berger
authors.forename: M
authors.initials: M
authors.lastname: Fiedler
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000009:adverse effects / Q000627:therapeutic use*; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D011446:Prospective Studies; D011788:Quality of Life; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D019258:Saquinavir / Q000627:therapeutic use*; D019562:Viral Load; D015215:Zidovudine / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D007376:Interleukin-2; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D019258:Saquinavir