Phase 2
Completed N=5
MMF for HIV Reservoir Reduction
Human Immunodeficiency Virus I Infection
Source: ClinicalTrials.gov NCT03262441 ↗
Enrolled (actual)
5
Serious AEs
20.0%
Results posted
Dec 2020
Primary outcomePrimary: Change in Cell-associated HIV DNA (Ca-DNA) Levels Per 10^6 T Cells Over 12 Months — -0.00033 log10 caDNA copies per 10^6 T-cells/week
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in Cell-associated HIV DNA (Ca-DNA) Levels Per 10^6 T Cells Over 12 Months |
-0.00033 | — |
| PRIMARY Change in Cell-associated HIV DNA (Ca-DNA) Levels Per 10^6 Effector Memory CD4+ T Cells Over 12 Months |
0.001 | — |
| PRIMARY Change in Cell-associated Intact HIV DNA (Ca-iDNA) Levels Per 10^6 T Cells Over 12 Months |
.0024 | — |
| SECONDARY Blood CD4+ T Cells Per mm^3 Blood |
— | — |
| SECONDARY Incidence of Opportunistic Infection |
— | — |
Eligibility Criteria
Inclusion Criteria
- Confirmed HIV infection, by two different positive antibody tests and/or detectable plasma HIV RNA on two different dates
- ≥18 and ≤65 years of age
- Continuous ART during the last two years, with current ART preferably including an integrase inhibitor
- HIV RNA 350/mm3 within the past 365 days
- Karnofsky score ≥80
- Plan to reside in area 2 years
- Consents to study
- Tolerability of MMF during one week dose escalation lead-in phase of 500 mg once daily
- Demonstrated anti-proliferative effect of MMF 500 mg twice daily
Exclusion Criteria
- Active malignancy including skin cancer, myelodysplastic syndrome, or myeloproliferative disease within 24 weeks prior to study entry
- Prior organ or bone marrow transplantation
- Diagnosed autoimmune disease
- Medical need for ongoing treatment with an immunosuppressive drug
- Diagnosis of AIDS (defined as any AIDS-defining opportunistic infection or cancer, or a history of blood CD4+ T cell count 8
- Substance abuse
- History of medical non-compliance
- Quantiferon TB positive
- The following laboratory values ( 2 x upper limit of normal
- Platelet count < 100,000/uL
- Creatinine clearance < 60 mL/min
Data sourced from ClinicalTrials.gov (NCT03262441). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.