Vedolizumab (Anti-alpha4beta7) in Subjects With HIV Infection Undergoing Analytical Treatment Interruption
Condition: HIV
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      In most people infected with human immunodeficiency virus (HIV), their immune system cannot
      control HIV infection. They need drugs called combination antiretroviral therapy (cART) to
      control the HIV. When people stop cART treatment, their immune system cannot control the
      infection again. They can also become resistant to cART and have lasting side effects.
      Researchers want to test if the drug vedolizumab is effective at controlling HIV infection
      without the need for cART.

      Objective:

      To test if vedolizumab is safe and can control the amount of HIV in the blood when cART is
      not taken.

      Eligibility:

      People ages 18-65 who have HIV and are being treated with cART

      Design:

      Participants will be screened with:

      Physical exam

      Medical history

      Electrocardiogram: Soft, sticky patches on the chest, arms, and legs measure heart activity.

      Blood and urine tests

      Participants will have a baseline visit. This will be 2-5 hours each day for 1-2 days. It
      will include repeats of the screening tests and:

      Leukapheresis: Blood is removed through a needle in the arm. A machine separates the white
      blood cells from the blood. The rest of the blood is returned to the participant.

      Neurologic exam: The nerves and reflexes are tested.

      First vedolizumab infusion through an arm vein

      Participants will have visits every 4 weeks for 30 weeks. These will include:

      Vedolizumab infusions

      Repeats of baseline tests

      Participants will have more visits for blood draws.

      Participants will keep taking cART until after the week 22 infusion.

      After discontinuing cART at study week 22, participants will be seen every two weeks to
      monitor the CD4 count and the level of HIV in the blood. Some of these visits will occur in
      between infusion visits and will only take about 1 hour to complete. cART will be restarted
      if a participant's HIV levels go up to high, or if their CD4 cell counts decreases by too
      much.

      For the follow-up phase, participants will have visits every 4 weeks for 24 weeks. These will
      include blood tests and a physical exam.

      ...
    

Detailed description: 
      While combination antiretroviral therapy (cART) has improved the clinical outcome for
      HIV-infected individuals, persistence of viral reservoirs in the peripheral blood and
      lymphoid tissues remains a hurdle to complete eradication of virus and cure of the infection.
      The concept that HIV preferentially infects discrete subsets of CD4+ T cells underscores the
      need to develop therapeutics that exploit specific cell-virus interactions. T cells
      expressing integrin alpha4beta7 not only regulate migration into the gut associated lymphoid
      tissue (GALT), but also concomitantly bind HIV, placing them in a prime position to
      disseminate HIV throughout the tissue. Previously, it has been shown that the HIV envelope
      protein gp120 binds to alpha4beta7 on CD4+ T cells in vitro, alpha4beta7high CD4+ T cells are
      highly susceptible to productive HIV infection in vitro, and the administration of
      anti-alpha4beta7 monoclonal antibody (mAb) prevents and/or delays transmission of SIV upon
      repeated challenges and preserves CD4+ T cells in rhesus macaques. Furthermore, it has been
      demonstrated that administration of anti-alpha4beta7 mAb in SIV-infected rhesus macaques
      receiving cART suppresses plasma viremia for extended periods following discontinuation of
      cART, collectively suggesting that sustained virologic remission in the absence of cART may
      be achieved via direct targeting of alpha4beta7 integrin. It is well established that the
      vast majority of HIV-infected individuals treated with cART experience plasma viral rebound
      within weeks of cessation of therapy. Considering that current research on the treatment of
      HIV-infected individuals has been heavily focused on developing strategies aimed at achieving
      sustained virologic remission in the absence of cART, it is of great interest to investigate
      whether administration of anti-alpha4beta7 mAb can prevent plasma viral rebound and allow
      durable suppression of viral replication in HIV infected individuals after discontinuation of
      cART. We propose to examine the effect of vedolizumab, an FDA approved anti-alpha4beta7 mAb
      for the treatment of ulcerative colitis and Crohn's disease, on plasma viral rebound in
      HIV-infected individuals following analytical treatment interruption (ATI).
    

Intervention name(s): Entyvio (Vedolizumab)
Intervention type(s): Biological
Intervention description(s): A humanized monoclonal antibody that specifically binds to the alpha4beta7 integrin with MAdCAM-1, which in turn inhibits the migration of T-lymphocytes across the endothelium into GALT
Intervention MeSH terms: Vedolizumab
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: HIV Immune Therapy; Monoclonal Antibody; Integrin