Study of the HIV gp120/NefTat/AS02A Vaccine to Treat Individuals With Chronic HIV-1 Infection on Highly Active Antiretroviral Therapy (HAART)
Condition: HIV Infections
MeSH terms: Infections; Communicable Diseases
Study type: Interventional
Phase: Phase 1

Summary: 
      This study will test the safety and immunogenicity of the gp120/NefTat/AS02A vaccine
      candidate in individuals with chronic HIV-1 infection successfully treated with HAART. The
      rationale for this study is based on previous scientific experiments, including data
      indicating that this vaccine can elicit strong HIV-1-specific T cell immune responses in
      humans and monkeys and lead to a retardation of HIV-1 disease progression in animal models of
      HIV-1 infection.

      The HIV vaccine to be administered during this study consists of three recombinant HIV clade
      B viral antigens: the envelope glycoprotein gp120 and two regulatory proteins, Nef and
      Tat.The antigens are formulated in a proprietary adjuvant, AS02A, comprised of two
      immunostimulants in an oil-in-water emulsion (gp120/NefTat/AS02A). The vaccine and the
      adjuvant are manufactured and provided for the study by GlaxoSmithKline Biologicals,
      Rixensart, Belgium. The drugs will be given by intramuscular (IM) injection at a standard
      dose of 20 mg together with 0.5 ml of the AS02A adjuvant.

      Twenty HIV-1 infected individuals will be randomly enrolled into three different study
      groups, receiving either the gp120/NefTat/AS02A vaccine (10 individuals), the AS02A adjuvant
      alone (5 individuals) or a placebo (5 individuals). After obtaining informed consent,
      subjects will have a history and physical exam performed and have laboratory tests to confirm
      they meet all inclusion and exclusion entry criteria. Women of childbearing potential will
      have a pregnancy test prior to each injection of the investigational product. Injections with
      vaccine, adjuvant alone, or placebo will then be performed at weeks 0, 4, and 12. Study
      participants will undergo close monitoring after each vaccination. Blood samples will be
      obtained for immunological assays at study baseline (2 times) and weeks 2, 4, 6, 12, 14, 24,
      and 48. All patients will maintain their antiretroviral treatment regimen during the entire
      study period.
    

Detailed description: 
      DESIGN: This study is a randomized, double blind clinical trial of the gp120/NefTat/AS02A
      vaccine in individuals with well-controlled chronic HIV-1 infection who have been
      successfully treated with highly active antiretroviral therapy (HAART). The adjuvanted
      protein vaccine candidate consists of three recombinant viral antigens: the envelope
      glycoprotein gp120 and two regulatory proteins, Nef and Tat. The latter are expressed as one
      recombinant fusion protein, NefTat. The antigens are formulated in the proprietary AS02A
      adjuvant. The goal of this trial is to assess the safety and immunogenicity of the
      gp120/NefTat/AS02A vaccine in HIV-1-infected individuals.

      DURATION: 48 weeks

      SAMPLE SIZE: 20 subjects

      POPULATION: Subjects with chronic HIV-1 infection receiving highly active antiretroviral
      therapy (HAART) with HIV RNA levels <50 copies/mL on at least two measurements in the
      previous 6 months and a CD4+ T cell count >400 cells/mm3 within 45 days of study entry will
      be eligible for this study.

      REGIMEN: Enrolled patients will be randomized to receive either the vaccine
      (gp120/NefTat/AS02A) (10 individuals), the AS02A adjuvant only (5 individuals) or a placebo
      (5 individuals). Injections will be administered IM at weeks 0, 4, and 12.

      OBJECTIVES: The two primary objectives of this study are:

        -  to evaluate the safety and tolerability of the gp120/NefTat/AS02A vaccine in individuals
           with well-controlled chronic HIV-1 infection on HAART; and

        -  to evaluate the cell-mediated immune response (IL-2 secreting CD4+ T cells) to at least
           one vaccinal antigen induced by the vaccine-adjuvant combination in individuals with
           chronic HIV-1 infection on successful HAART, at two weeks after the third vaccination.

      ENDPOINTS: The two co-primary study endpoints will be:

        -  the occurrence, intensity, and relationship of any local and general signs and symptoms
           during a 7-day follow-up period after each vaccination (primary safety endpoint); and

        -  the changes in the frequency of IL-2 secreting CD4+ T cells in response to at least one
           vaccinal antigen (primary immunogenicity endpoint) in the three different patient
           categories, assessed two weeks after the third vaccination.
    

Intervention name(s): HIV gp120/NefTat/AS02A Vaccine
Intervention type(s): Biological
Intervention description(s): im injection, 0.6-0.7 ml
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: HIV-1; therapeutic vaccination; cellular immunity; humoral immunity; HAART; chronic HIV-1 infection; Treatment Experienced; HIV Therapeutic Vaccine