MMF for HIV Reservoir Reduction

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.

Timeline

Start

2018-02-12

Primary completion

2019-08-31

Completion

2019-08-31

Publications

• Background Reeves DB, Duke ER, Hughes SM, Prlic M, Hladik F, Schiffer JT. Anti-proliferative therapy for HIV cure: a compound interest approach. Sci Rep. 2017 Jun 21;7(1):4011. doi: 10.1038/s41598-017-04160-3.
• Schiffer JT, Levy C, Hughes SM, Pandey U, Padullo M, Jerome KR, Zhu H, Puckett K, Helgeson E, Harrington RD, Hladik F. Stable HIV Reservoir Despite Prolonged Low-Dose Mycophenolate to Limit CD4+ T-cell Proliferation. Open Forum Infect Dis. 2022 Nov 19;9(12):ofac620. doi: 10.1093/ofid/ofac620. eCollection 2022 Dec.

Drugs

Indications