Therapeutic Vaccine for HIV
Condition: HIV; Therapeutic Vaccine
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      - In most people who have human immunodeficiency virus (HIV), the immune system cannot
      control or cure the infection. Antiretroviral therapy drugs can keep the amount of HIV virus
      low for a long time. However, this treatment does not remove the virus from the body. In the
      vast majority of patients antiretroviral therapy also will not protect the body from the
      virus once treatment stops. Researchers want to see if therapeutic vaccination can help
      people with HIV. Therapeutic vaccination means giving vaccines to treat an infection that
      someone already has (HIV, in this case). It may help the body's immune system attack the
      infection. This study will look at different measures of HIV infection after receiving either
      therapeutic vaccination or a placebo.

      Objectives:

      - To see whether therapeutic vaccination is safe and can affect how the body responds to HIV
      infection.

      Eligibility:

      - Individuals between 18 and 65 years of age who have HIV and are taking antiretroviral
      therapy drugs.

      Design:

        -  Participants will be screened with a physical exam and medical history. Blood and urine
           samples will be collected.

        -  During the screening visit and throughout the study until week 56, participants will
           continue to take their HIV medications.

        -  Participants will be divided into two groups. One group will have the study vaccines.
           The other will have a placebo.

        -  The first study vaccine or placebo will be given in weeks 4, 12, and 36. The second
           study vaccine or the placebo will be given in weeks 24 and 48. Blood samples and other
           tests will be given at each visit.

        -  After the study visit at week 56, participants will stop their HIV medications until
           week 72. From weeks 58 through 72, they will come in every 2 weeks for study visits;
           each visit will take about 1 hour to complete. These visits will look at the body s
           response to the vaccines and their HIV viral load. After week 72, participants will
           re-start their HIV medications.

        -  There will be follow-up study visits from weeks 76 to 96, with blood tests and other
           studies.
    

Detailed description: 
      The advent of combination antiretroviral therapy (cART) has dramatically improved the
      clinical outcome in human immunodeficiency virus (HIV)-infected individuals through sustained
      reduction in viral replication. However, it has become clear that cART alone cannot eradicate
      HIV in infected individuals, likely in part due to the persistence of viral reservoirs in
      peripheral blood and various tissue compartments. Consequently, a major thrust of HIV
      research over the past several years has been to develop therapeutic strategies that can
      eliminate persistent viral reservoirs and boost host immunity to control viral replication
      upon discontinuation of cART. Therapeutic HIV vaccination is one approach that could
      potentially achieve these goals through vaccine-induced improvement in HIV-specific immune
      responses and/or by direct reactivation of HIV-specific CD4+ memory T cells that harbor
      latent HIV. An effective therapeutic vaccine could augment immunologic control of HIV
      infection and potentially obviate the need for chronic cART.

      The current study is an exploratory randomized, 2-arm (1:1), double-blind, placebo-controlled
      trial evaluating the safety and efficacy of an HIV-1 multiantigen plasmid DNA (HIV-MAG pDNA)
      vaccine prime in combination with an interleukin-12 plasmid DNA (IL-12 pDNA) adjuvant
      delivered by in vivo electroporation followed by a recombinant vesicular stomatitis virus
      vector containing the HIV-1 gag gene (rVSV HIV gag) booster vaccine in subjects on cART who
      started therapy during acute or early HIV infection.

      Subjects will be randomized to receive placebo or the HIV-MAG pDNA (3000 g) vaccine prime and
      IL-12 pDNA adjuvant (1000 g) at week 0, 4, 12, and 36, and the rVSV HIV gag booster vaccine
      (1x107 plaque-forming units) at week 24 and 48. The HIV-MAG pDNA vaccine prime and IL-12 pDNA
      adjuvant will be administered as 2 IM injections, 1 into each deltoid, with electroporation
      using the Ichor TDS device, while the rVSV HIV gag booster vaccine will be administered as 2
      conventional IM injections, 1 into each deltoid. After the week 56 visit, all subjects will
      undergo an analytical treatment interruption to determine if the vaccination strategy results
      in an improved immune control of viral replication, as evidenced by a blunted or absent
      rebound in HIV plasma viremia. All subjects will be followed through week 96 for safety and
      efficacy parameters.

      The study population includes HIV-infected adults who began cART during acute or early
      infection. Subjects must be receiving an effective cART regimen, with a CD4 cell count of
      >450 cells/mm3 at screening, and they must have documented viral suppression below the limit
      of detection for greater than1 year. The rationale for testing the study vaccine regimen in
      this subject population is because these individuals may have a relatively preserved immune
      function, which could be augmented by therapeutic vaccination.
    

Intervention name(s): rVSV; IL-12 pDNA adjuvant; HIV-Mag pDNA; Placebo
Intervention type(s): Biological; Biological; Biological; Drug
Intervention description(s): Attenuated recombinant vesicular stomatitis virus containing HIV-1 gag gene; plasmid DNA containing human IL-12 gene; plasmid DNA vaccine containing genes encoding multiple HIV-1 proteins
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: HIV-MAG pDNA Prime; HIV Therapy; Therapeutic Vaccine