MMF for HIV Reservoir Reduction

• Status: Completed
• Trial end date: 2019-08-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Fred Hutchinson Cancer Research Center
• Collaborator: University of Washington
• Treatments: Mycophenolate mofetil; Mycophenolic Acid

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