Immunization With HIV-1 Peptides in Adjuvant for Treatment of Patients With Chronic HIV-infection
Condition: HIV INFECTIONS
MeSH terms: Infections; HIV Infections; Acquired Immunodeficiency Syndrome
Study type: Interventional
Phase: Phase 1

Summary: 
      Treatment: Immunization with a peptide-mix of 17 Clusters of Differentiation number 8 (CD8) T
      cell minimal epitopes and 3 Clusters of Differentiation number 4 (CD4) T cell epitopes and a
      new adjuvant (CAF01). The vaccine should induce cellular immunity against human
      immuno-deficiency virus type-1 (HIV-1).

      Target group: Untreated healthy individuals with chronic HIV-1 infection who are not in
      antiretroviral treatment.

      Purpose: The primary purpose is to evaluate tolerability and safety of the vaccine.

      The secondary purpose is to evaluate the clinical effect of the vaccination treatment as
      measured by induction of new T cell immunity, lowering of HIV-1 ribonucleic acid (RNA) viral
      load in plasma, and improvement in the patient CD4 lymphocyte blood counts.

      Design: The experiment is designed as a single-blinded, placebo-controlled phase 1 clinical
      trial in HIV-1 infected individuals in Denmark.

      Numbers of individuals: 20 fully evaluable HIV-1-infected patients should enter the study (15
      vaccine treated and 5 placebo(saline) treated controls).

      The hypothesis is that a redirection of cytotoxic T lymphocyte (CTL) immunity to selected
      relatively immune silent (subdominant) but conserved CTL targets on multiple sites in HIV-1
      could provide a better immune control of the virus replication. This could result in lowering
      of viral load thereby prolonging the time to antiretroviral therapy.
    

Detailed description: 
      The HIV-1 vaccine in this trial is designed to prevent disease in healthy already HIV-1
      infected individuals not in anti-retroviral treatment by inducing a strong cellular immune
      response against several immune subdominant selected target points in the patient's HIV-1
      virus. The vaccine treatment is not harmful but could potentially lower viral load and thus
      delay the time to acquired immuno deficiency syndrome (AIDS) disease or to the need of
      antiviral medicine and thereby limit the spread of HIV-1 in the population.

      The patient's cellular immune response can only partly control the HIV-1 infection and
      eventually leads to a destruction of the immune system, opportunistic infections, and
      ultimately death. Normally the natural HIV-1 infection does not provide adequate immunity and
      vaccines must therefore induce a more potent and broader and more rationally directed
      immunity. Individuals that have this kind of strong immunity have lower viral-load and live
      longer. The vaccine in this study is designed to develop this kind of potent cellular
      immunity against HIV-1, so the virus is controlled better by the individual and spread in the
      population is limited.

      This vaccine is designed to match most individual's cellular immune system (HLA tissue types)
      and several conserved target points in the individual's own HIV-1 virus. On the basis of our
      previous vaccine trial of HIV vaccination of HIV-infected individuals in Denmark and years of
      research, we have been able to develop this HIV-1 vaccine. Our vaccine contains 18 peptides
      (15 major histocompatibility complex class 1 (MHC-I) restricted CD8-t-cell epitopes and 3 MHC
      class-II restricted CD4 T-cell epitopes) in a mix and should induce cellular immune responses
      to several conserved target points identified in HIV-1. Our vaccine is composed of 18
      peptides in a lipid based adjuvant Cationic Adjuvant Formulation number 1 (CAF01) composed of
      dimethyl-deoctadecylammonium (DDA) and trehalose-dibehenate (TDB) and is deemed safe and the
      technique is simple and also called 'peptide vaccination'. This and similar techniques have
      been tried in several studies against virus diseases around the world.

      We want to know to which degree it is possible to immunize already HIV¬ 1 infected
      individuals to prolong the healthy period and prevent disease before initiation of antiviral
      medicine or other treatments of AIDS. In the present immunization study, healthy HIV-1
      infected individuals not in treatment in Denmark will be invited to participate. This vaccine
      study will examine the immune responses and effects of the vaccine on these healthy
      HIV-1-infected individuals. The first purpose is first to determine if there are any
      side-effects of the vaccine. From several trials on animals and humans and in our own recent
      HIV vaccination trial on HIV-1 infected individuals in Denmark, with very similar vaccine
      techniques (peptides in autologous Dendritic Cells (DC) no serious side-effects has been
      observed. The second purpose is to examine if the vaccine induces the expected immune
      responses in HIV-1 infected individuals and how it enforces and supplements the already
      existing 'own' immune response of the infected individual. Finally, a clinical beneficial
      effect (on viral load and CD4 counts) of our vaccine will be evaluated.
    

Intervention name(s): peptide vaccine (AFO-18)
Intervention type(s): Biological
Intervention description(s): 18 Peptides (250 ug of each peptide) in Adjuvant CAF01 (= 625/125 ug DDA/TDB), i.m. injection week 0, 2, 4, 8.
Other intervention name(s): DDA/TDB; peptides
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: VACCINE; THERAPY; CELLULAR IMMUNITY; IMMUNITY