MMF for HIV Reservoir Reduction
Condition: Human Immunodeficiency Virus I Infection
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections
Intervention: Mycophenolate Mofetil 500Mg Tab
Intervention description: 500 mg once daily for one week. If tolerating the drug, then initiate twice daily for 22 months
Intervention MeSH terms: Mycophenolic Acid
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
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)
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: HIV; Antiretroviral treatment; Mycophenolate mofetil; Cure; Latency; Reservoir; CD4 T cell; Anti-proliferation

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Confirmed HIV infection, by two different positive antibody tests and/or detectable
             plasma HIV RNA on two different dates

          2. ≥18 and ≤65 years of age

          3. Continuous ART during the last two years, with current ART preferably including an
             integrase inhibitor

          4. HIV RNA <40 copies / mL on four occasions during continuous ART of ≥ 2 years with no
             more than one blip of <1000 HIV RNA copies / mL

          5. CD4+ T cell count > 350/mm3 within the past 365 days

          6. Karnofsky score ≥80

          7. Plan to reside in area 2 years

          8. Consents to study

          9. Tolerability of MMF during one week dose escalation lead-in phase of 500 mg once daily

         10. Demonstrated anti-proliferative effect of MMF 500 mg twice daily

        Exclusion Criteria:

          1. Active malignancy including skin cancer, myelodysplastic syndrome, or
             myeloproliferative disease within 24 weeks prior to study entry

          2. Prior organ or bone marrow transplantation

          3. Diagnosed autoimmune disease

          4. Medical need for ongoing treatment with an immunosuppressive drug

          5. Diagnosis of AIDS (defined as any AIDS-defining opportunistic infection or cancer, or
             a history of blood CD4+ T cell count < 200/µL)

          6. Active opportunistic infection

          7. Using disallowed medications (see 4.3)

          8. Vomiting or diarrhea which prohibits consistent use of study drugs

          9. Pregnant, intention to become pregnant, or breastfeeding

         10. Woman of child bearing age who are NOT using two forms of birth control OR practicing
             complete abstinence

         11. Excessive ingestion of ethanol, determined by an AUDIT score of >8

         12. Substance abuse

         13. History of medical non-compliance

         14. Quantiferon TB positive

         15. The following laboratory values (< 30 days before enrollment):

               -  Hemoglobin < 8.5 mg/dL

               -  Absolute neutrophil count < 1000 cells/mm3

               -  ALT > 2 x upper limit of normal

               -  Platelet count < 100,000/uL

               -  Creatinine clearance < 60 mL/min