NCT03262441

MMF for HIV Reservoir Reduction

Mycophenolate Mofetil Therapy for Reduction of the HIV Reservoir

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 5 (actual)
• Sponsor: Fred Hutchinson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Human Immunodeficiency Virus I Infection

Interventions

Type	Name	Description
DRUG	Mycophenolate Mofetil 500Mg Tab	500 mg once daily for one week. If tolerating the drug, then initiate twice daily for 22 months

Timeline

• Start date: 2018-02-12
• Primary completion: 2019-08-31
• Completion: 2019-08-31
• First posted: 2017-08-25
• Last updated: 2020-12-03
• Results posted: 2020-12-03

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study