Safety and Efficacy of Allogenic Adoptive Immune Therapy for Advanced AIDS Patients
Condition: Human Immunodeficiency Virus; Immunodeficiency
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections; Immunologic Deficiency Syndromes
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Combined antiretroviral therapy (cART) efficiently suppress viral replication in majority of
      AIDS patients. The morbidity and mortality of the disease has dramatically decreased over the
      past 20 years. However, chronic human immunodeficiency virus-1 (HIV-1) infection lead to
      profound immune defects in some advanced AIDS patients who often develop with severe
      opportunistic infections (OIs), severe cachexia and other deadly complications, which
      accounts for the major death group even under cART. Up-to-date, there are no effective immune
      interventions to restore host holistic immunity for advanced AIDS patients.
    

Detailed description: 
      Advanced AIDS patients are usually characterized with CD4 T cells less than 200 cells/uL,
      including end-stage AIDS patients (CD4 T cells less than 50 cells/uL), and often accompanied
      with severe opportunistic infections (including tuberculosis, PCP, fungus and so on) and
      deadly complications.In this regard, advanced AIDS patients present a unique and special
      profound immune deficiency setting. Therefore, increasing attention and evidence have been
      paid to development of novel immune therapeutic strategies for those patients.

      Immune cell therapy in combination with anti-infection and anti-HIV therapy may open a new
      direction for advanced AIDS patients, but single cell-based immune therapies do not work well
      for advanced AIDS patients. Over past 30 years, more than hundreds of AIDS patients with
      haematological malignancies received autologous or allogeneic hematopoietic stem cell
      transfusion (HSCT), and their survival rate had been improved to the levels equal to non-HIV
      patients; however, allogeneic HSCT is only limited to treat AIDS patients with lymphoma or
      leukemia. The only cured Berlin Patient, who suffered from both acute myeloid leukemia and
      chronic HIV-1 infection, was transplanted with homozygous CCR5 delta 32 allogeneic
      HLA-matched stem cells and acquired a long-term remission of both leukemia and AIDS. However,
      it is very difficult to find the HLA-identical HSCT with CCR5 delta 32 homogenous donors for
      AIDS patients in clinic. Granulocyte colony-stimulating factor (G-CSF)-mobilized donor
      peripheral blood mononuclear cells (MNCs) are a heterogeneous population of immune cells that
      have a potential role in immunomodulation and hemopoiesis. Here, we hypothesized that
      HLA-mismatched MNCs transfusion can be used to comprehensively restore or boost the host
      holistic immune system for advanced AIDS patients, to the degree similar as the allogeneic
      HSCT for leukemia patients.

      The purpose of this study is to investigate the safety and initial efficacy of allogeneic
      adoptive immune therapy (AAIT) for advanced AIDS patients. 20 patients received i.v.
      transfusion one round (3 times) of 2.0-3.0*10E8 cells/kg of MNSs as the treated group. All of
      them received the conventional (anti-opportunistic infection and ART) treatment for AIDS. The
      side effects, symptom improvement, control of opportunistic infections and CD4 T cell numbers
      will be evaluated during the 48-week follow up.
    

Intervention name(s): Conventional plus AAIT
Intervention type(s): Combination Product
Intervention description(s): Participants received conventional (anti-opportunistic infections and ART) treatment and taken i.v., at a roud (3 times) of 2-3*10E8 MNCs/kg body at baseline, week 1 and 2.
Other intervention name(s): Conventional plus allogeneic adoptive immune treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Immunodeficiency; Allogenic Mononuclear Cell Transplantation