Safety and Immune Response to a Prime-Boost Vaccination Schedule in HIV-infected Patients
Condition: HIV
Study type: Interventional
Phase: Phase 1

Summary: 
      Study Design: This is a Phase I, randomized, placebo-controlled, double-blinded study to
      examine safety, tolerability and immune response of a prime-boost vaccination regimen for
      treatment of HIV infection. The vaccination schedule consists of three injections of a
      multiclade HIV plasmid DNA vaccine followed by one injection of a multiclade recombinant
      adenoviral vector vaccine (rAd), in HIV-infected adults. The hypothesis is that this
      vaccination regimen will be safe and elicit an immune response in HIV-infected subjects. The
      primary objectives are related to evaluating the safety and tolerability of the vaccination
      regimen and assessing the effect of vaccination on humoral and cellular immune responses to
      vaccine-specific HIV antigens.

      Product Description: VRC-HIVDNA016-00-VP is composed of 6 closed, circular DNA plasmids that
      are each 16.67% (by weight) of the vaccine. Each of the 6 plasmids in this vaccine expresses
      a single gene product. Plasmids VRC 4401, VRC 4409 and VRC 4404 are designed to express clade
      B HIV-1 Gag, Pol and Nef, respectively. VRC 5736, VRC 5737, and VRC 5738 are designed to
      express HIV-1 Env glycoprotein from clade A, clade B, and clade C, respectively. Each DNA
      vaccination will be 1 mL of vaccine administered intramuscularly (IM) using the Biojector
      2000 Needle-Free Injection Management System. Phosphate buffered saline (PBS) will be used as
      the placebo for the DNA vaccine.

      VRC-HIVADV014-00-VP (rAd) is a recombinant product composed of 4 adenoviral vectors (Ad) (in
      a 3:1:1:1 ratio) that encode the HIV-1 Gag/Pol polyprotein from clade B and HIV-1 Env
      glycoproteins from clades A, B, and C, respectively. Injections of 10(10) PU will be
      administered IM by needle and syringe. The final formulation buffer (FFB) will be used as the
      placebo for the rAd vaccine.

      Subjects: HIV-infected adult volunteers (18-50 years old) on stable highly active
      antiretroviral therapy (HAART) therapy who have a CD4+ cell count greater than 350 cells/mm3
      and have had a viral load (VL) less than 400 copies/mL for at least six months and a viral
      load of less than 50 copies/mL within 4 weeks prior to enrollment.

      Study Plan: Fifteen volunteers will be enrolled and randomized in a 2:1 ratio to
      vaccine:control (10 DNA prime with rAd boost:5 PBS with FFB placebo). A Data and Safety
      Monitoring Board (DSMB) will review the study every 6 months. Subjects will be evaluated for
      safety and immunogenicity for 48 weeks, which is 24 weeks after the target date for the
      booster vaccination.

      Study Duration: Subjects will be followed for 48 weeks after enrollment into the study.
    

Detailed description: 
      This study will determine the safety and side effects of two experimental HIV vaccines and
      see if vaccination can enhance the pre-existing HIV-specific immune response in HIV-infected
      individuals on anti-retroviral therapy . The vaccines are VRC-HIVDNA016-00-VP (called the
      "DNA vaccine") and VRC-HIVADV014-00-VP (called the "rAd vaccine"). The DNA vaccine codes for
      four HIV proteins. The rAd vaccine is made using an adenovirus (a common virus that causes
      upper respiratory infections, such as the common cold) that has been modified to contain DNA
      that codes for three HIV proteins. These vaccines will be given in a "prime-boost" schedule
      and cannot cause HIV or adenoviral infections.

      HIV-infected people between 18 and 50 years old who are on a stable treatment plan for HIV
      with highly active antiretroviral (ARV) drugs, have a CD4+ T cell count greater than 350, and
      have a low viral load may be eligible for this 48-week study.

      Participants receive an injection (shot) of the DNA vaccine or a placebo (solution that does
      not contain any vaccine, medicine, or drugs) the day they enter the study and again at study
      weeks 4 and 8. They receive a booster injection of the rAd vaccine or placebo at week 24. The
      DNA vaccines are given with a needle-less injection device called the "Biojector
      2000(Registered Trademark)" and the rAd vaccine is given using a needle and syringe. All
      shots are given in the upper arm muscle, alternating right and left arms with each injection.
      Patients fill out a diary card at home for 5 days after each vaccination, recording their
      temperature and any symptoms. The cards are turned in to the clinic at the first visit after
      all 5 days are completed. Patients must call a study nurse 1 or 2 days after each of the four
      injections and again 7 or 8 days after each of the first three injections.

      Patients have 12 clinic visits during the course of the study. At each visit, they are
      checked for health changes or problems, asked how they are feeling and if they have taken any
      medications or other treatments, including over-the-counter medicines, herbal supplements,
      etc. Blood samples are drawn at every visit and urine samples are collected at some visits.

      At week 28 (4 weeks after the fourth injection), patients undergo apheresis, a procedure for
      collecting large numbers of white blood cells. The cells are tested in the laboratory to see
      how the immune system responds to the study vaccine. For the procedures, blood is collected
      through a needle in an arm vein and spun in a machine that separates the white blood cells
      from the rest of the blood (red cells, plasma and platelets). The white cells are removed and
      the rest of the blood is returned to the patient's body through the same needle. Patients who
      cannot or do not want to undergo apheresis have 80 mL (about 1/3 cup) of blood drawn through
      a needle and collected in blood collection tubes.
    

Intervention name(s): VRC-HIVDNA016-00-VP; VRC-HIVADV014-00-VP
Intervention type(s): Drug; Drug
Primary purpose: Treatment
Keywords: HIV-positive; Treatment Interruption; Therapeutic Vaccine; HIV/AIDS; Virologic Response; HIV Positive