title: A phase I, randomized study of combined IL-2 and therapeutic immunisation with antiretroviral therapy.
abstract: BACKGROUND
  Fully functional HIV-1-specific CD8 and CD4 effector T-cell responses are vital to the containment of viral activity and disease progression. These responses are lacking in HIV-1-infected patients with progressive disease. We attempted to augment fully functional HIV-1-specific CD8 and CD4 effector T-cell responses in patients with advanced chronic HIV-1 infection.
  
  
  METHODS
  Chronically infected patients with low CD4 counts T-cell counts who commenced antiretroviral therapy (ART) were subsequently treated with combined interleukin-2 and therapeutic vaccination.
  
  
  METHODS
  Thirty six anti-retroviral naive patients were recruited and initiated on combination ART for 17 weeks before randomization to: A) ongoing ART alone; B) ART with IL-2 twice daily for 5 days every four weeks starting at week 17 for 3 cycles; C) ART with IL-2 as in group B and Remune HIV-1 vaccine administered once every 3 months, starting at week 17; and D) ART with Remune vaccine as in group C. Patients were studied for 65 weeks following commencement of ART, with an additional prior 6 week lead-in observation period. CD4 and CD8 T-cell counts, evaluations of HIV-1 RNA levels and proliferative responses to recall and HIV-1 antigens were complemented with assessment of IL-4-secretion alongside quantification of anti-HIV-1 CD8 T-cell responses and neutralizing antibody titres.
  
  
  RESULTS
  Neither IL-2 nor Remune vaccination induced sustained HIV-1-specific T-cell responses. However, we report an inverse relationship between HIV-1-specific proliferative responses and IL-4 production which continuously increased in patients receiving immunotherapy, but not patients receiving ART alone.
  
  
  CONCLUSIONS
  Induction of HIV-1-specific cell-mediated responses is a major challenge in chronically HIV-1-infected patients even when combining immunisation with IL-2 therapy. An antigen-specific IL-4-associated suppressive response may play a role in attenuating HIV-specific responses.
authors.affiliation: Department of Immunology, Imperial College London, Chelsea and Westminster Hospital, 369 Fulham Road, London, SW10 9NH, UK.
authors.forename: Gareth Ad
authors.initials: GA
authors.lastname: Hardy
authors.affiliation: Department of Immunology, Imperial College London, Chelsea and Westminster Hospital, 369 Fulham Road, London, SW10 9NH, UK.
authors.forename: Nesrina
authors.initials: N
authors.lastname: Imami
authors.affiliation: Department of HIV/GU Medicine, Imperial College London, Chelsea and Westminster Hospital, 369 Fulham Road, London, SW10 9NH, UK.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Nelson
authors.affiliation: Department of HIV/GU Medicine, Imperial College London, Chelsea and Westminster Hospital, 369 Fulham Road, London, SW10 9NH, UK.
authors.forename: Ann K
authors.initials: AK
authors.lastname: Sullivan
authors.affiliation: Immune Response Corporation, Carlsbad, CA, USA.
authors.forename: Ron
authors.initials: R
authors.lastname: Moss
authors.affiliation: Wohl Virion Centre, Windeyer Institute of Medical Sciences, UCL, London, W1T 4JF, UK.
authors.forename: Marlén Mi
authors.initials: MM
authors.lastname: Aasa-Chapman
authors.affiliation: Department of HIV/GU Medicine, Imperial College London, Chelsea and Westminster Hospital, 369 Fulham Road, London, SW10 9NH, UK.
authors.forename: Brian
authors.initials: B
authors.lastname: Gazzard
authors.affiliation: Department of Immunology, Imperial College London, Chelsea and Westminster Hospital, 369 Fulham Road, London, SW10 9NH, UK.
authors.forename: Frances M
authors.initials: FM
authors.lastname: Gotch