MMF for HIV Reservoir Reduction
Condition: Human Immunodeficiency Virus I Infection
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections
Study type: Interventional
Phase: Phase 2

Summary: 
      This is an open label, randomized Phase II study to determine whether Mycophenolate mofetil
      (MMF) given over 22 months meaningfully decreases the size of participants' HIV reservoir.

      In addition to primary safety endpoints, the following hypotheses regarding drug efficacy
      will be tested:

        1. MMF will be well tolerated and will not decrease adherence to or antiviral efficacy of
           ART.

        2. Peripheral CD4+ T-cell counts and percentages will not meaningfully decrease during
           treatment with MMF and ART.

        3. There will be no excess risk of opportunistic infections in MMF-treated study
           participants.

        4. MMF therapy will lead to a progressive decrease in reservoir size over 22 months of
           treatment.

        5. MMF therapy will lead to a continual shift in HIV reservoir composition from primarily
           effector memory CD4+ T cells (TEM) and central memory CD4+ T cells (TCM), to primarily
           stem cell like memory (TSCM) and naïve (TN) CD4+ T cells.

        6. MMF will eliminate detectable measures of the HIV reservoir, including by
           cell-associated DNA/mRNA and quantitative viral outgrowth.

        7. MMF will not decrease the humoral immune response to routine annual influenza
           vaccination.
    

Detailed description: 
      This is an open-label, randomized pilot trial to determine whether MMF given over 22 months
      meaningfully decreases the size of the HIV reservoir.

      At the University of Washington in Seattle, investigators will enroll 5 study participants
      who have been on ≥2 years of suppressive ART. Study participants will be followed closely for
      at least 22 months with safety labs and serial measurements of the HIV reservoir
      (specifically, cell-associated HIV DNA and mRNA (ca-DNA & ca-RNA), quantitative viral
      outgrowth assay (QVOA), and single copy plasma viral load (scVL)). A "go/no-go" decision will
      occur after 12 months based on pre-defined thresholds of reduction in the HIV reservoir
      measured with ca-DNA.

      All participants will be offered enrollment in a sub-study in which an anoscopy with rectum
      biopsies is performed on 3 occasions to assess the reservoir in the gastrointestinal
      lymphatic tissue (GALT).

      Investigators will vaccinate study participants with the annual influenza vaccine and analyze
      their humoral response to this vaccine approximately one month later with a routine blood
      draw done in conjunction with a safety labs blood draw.

      Investigators hypothesize that low doses of MMF will be well tolerated among healthy
      HIV-infected study participants who have fully ART-suppressed HIV. Investigators hypothesize
      that the incidence of opportunistic infections will not exceed that of comparable larger
      cohorts of HIV-treated patients. Of note, certain opportunistic infections such as herpes
      zoster or HSV-2 recurrence continue to occur despite suppressive ART, while pneumocystis
      pneumonia, CMV end organ disease, cryptococcus and many other opportunistic infections are
      much less common in this context. Therefore, in the event of an infection, Investigators will
      confer with the data safety management (DSM) panel to discuss whether this event is directly
      attributable to MMF. Finally, investigators hypothesize that peripheral blood CD4+ and CD8+ T
      cell counts will remain unchanged throughout MMF therapy, and that HIV replication will
      remain controlled on ART with addition of MMF.

      Investigators hypothesize at least a 0.25-log reduction in cell-associated HIV DNA at
      one-year intervals in study participants who have a demonstrated anti-proliferative response
      to MMF treatment. Investigators hypothesize that cell-associated HIV DNA will undergo a shift
      from predominant residence in TCM and TEM to predominant residence in TN and TSCM. In regards
      to our sub-study, investigators predict that reservoir depletion will occur with equivalent
      rates in blood and GALT.
    

Intervention name(s): Mycophenolate Mofetil 500Mg Tab
Intervention type(s): Drug
Intervention description(s): 500 mg once daily for one week. If tolerating the drug, then initiate twice daily for 22 months
Other intervention name(s): Mycophenolate Mofetil Tablets USP Roxane Laboratories
Intervention MeSH terms: Mycophenolic Acid
Intervention model: Single Group Assignment
Intervention model description: This is an open-label, randomized pilot trial to determine whether MMF given over 22 months meaningfully decreases the size of the HIV reservoir. Study participants will be followed closely for at least 22 months with safety labs and serial measurements of the HIV reservoir (specifically, cell-associated HIV DNA and mRNA (ca-DNA & ca-RNA), quantitative viral outgrowth assay (QVOA), and single copy plasma viral load (scVL)). "Go/no-go" decision will occur after 12 months based on pre-defined thresholds of reduction in the HIV reservoir measured with ca-DNA.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: HIV; Antiretroviral treatment; Mycophenolate mofetil; Cure; Latency; Reservoir; CD4 T cell; Anti-proliferation