MMF for HIV Reservoir Reduction

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.

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