AEGiS-14IAC: The effects of immunotherapy with cytokine and/or vaccine in HAART treated patients.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

The effects of immunotherapy with cytokine and/or vaccine in HAART treated patients.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. ThOrA1483)

Gotch FM, Hardy G, Imami N, Sullivan A, Nelson M, Burton C, Lopez JP, Moss R, Gazzard B
Imperial College of Science, Technology and Medicine, London, United Kingdom

BACKGROUND: Failure of HIV.1 specific CD4 helper T lymphocyte (HTL) and CD8 cytotoxic T lymphocyte (CTL) responses to re-emerge following successful diminution of plasma viraemia with HAART, has necessitated studies of novel immunotherapeutic approaches.

METHODS: A randomised, phase 1 study of HAART with or without IL2 and/or an inactivated gp120 depleted HIV.1 immunogen (Remune) was conducted in chronically infected patients with a mean baseline CD4 T cell count of 303 cells/ul blood. 36 patients were treated with HAART for 16 weeks before randomisation to: HAART alone; HAART + IL2; HAART + IL2 + Remune; HAART + Remune. CD4 responses to HIV antigens, recall antigens and mitogens were assessed, CTL responses measured by Elispot assays, levels of MIP1a in plasma were measured, TREC levels were quantified, phenotypic analysis was undertaken and CD4 T cell numbers and viral loads were monitored.

RESULTS: HAART alone was insufficient to allow regeneration of HIV-specific responses. IL2 therapy resulted in improved CD4 HTL responses to recall antigens, substantially increased CD4 T cell counts and induced transient viraemia which was less marked in patients receiving Remune with IL2. TREC levels were significantly reduced in patients receiving IL2. No changes were seen in plasma MIP.1a levels in any patients. No differences were seen in the induction of HIV specific HTL or CTL responses in groups receiving IL2 and/or Remune despite an apparently protective effect against virological events by their combination. In patients who experienced therapeutic failure in the context of immunotherapy leading to virological breakthrough, strong CD4 HTL and CD8 CTL responses to HIV were induced.

CONCLUSIONS: Transient regeneration of HIV specific immune responses could be induced by IL2 ± Remune. Autoimmunisation in the context of immunotherapy led to the most promising responses.

Keywords: AEGIS, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, AIDS Vaccines, HIV-1, HIV Infections, Cytokines, Immunotherapy, Viral Load, Anti-HIV Agents, HIV, Antigens, CD4, Interleukin-2, HIV Antigens, T-Lymphocytes, Helper-Inducer, T-Lymphocytes, Antigens, CD8, Viremia, T-Lymphocytes, Cytotoxic, remune, Human, immunology

020707
ThOrA1483