Oral Auranofin for Reduction of Latent Viral Reservoir in Patients With HIV Infection

The investigators proposed a novel approach in order to reduce the HIV viral reservoir. This
approach exploits the effects of auranofin, a gold based compound which has been used in the
treatment of rheumatoid arthritis. Auranofin induces partially selective apoptosis and
differentiation towards short-lived phenotypes of the T lymphocyte memory subsets that
encompass the main viral reservoir in patients. The hypothesis is that the targeted memory
cells would either die or decrease their persistence in the body, with the associated latent
viral reservoir being reduced.

The study will be conducted in two phases: A sequential dose-escalation phase to evaluate
two doses of auranofin, followed by an expansion at the maximum tolerated dose (MTD). A
total of 20 patients are to be treated at the MTD. Auranofin treatment is administered for
12 weeks.

Safety and tolerability will be evaluated by repeated laboratory panel and physcial
examination during the 12 weeks of auranofin therapy and 8 for weeks thereafter. The latent
reservoir will be measured by assessment of the inegrated viral DNA in CD4+ cells in the
circulating blood and in gut biopsies.

Inclusion Criteria:

- Participant is willing and able to give informed consent for participation in the
study.

- Male or female, between 18 and 55 years of age.

- Stable dose of ART (defined as at least 2 nucleoside/nucleotide reverse transcriptase
inhibitors plus a non-nucleoside reverse transcriptase inhibitor, integrase
inhibitor, or a protease inhibitor) for at least 2 years from study consent and with
no modifications expected during the study.

- HIV plasma viral load <50 copies/ml for at least 3 years with several measurements
per year and most recent viral load within 3 months of screening.8

- No previous failure of ART, understood as a rebound in viral load that can be
detected after having reached undetectable levels. Low-grade increases (<200 copies
of HIV RNA/mL) and transitory increases (blips) resolved without modifying ART are
acceptable.

- Did not experience AIDS defining event

- Two CD4+ T cell counts greater than 500 cell/µl in the six months prior to screening

- Able (in the Investigators' opinion) and willing to comply with all study
requirements.

Exclusion Criteria:

- Contraindication to auranofin therapy, including congestive heart failure, renal
dysfunction, history of blood dyscrasias; History of gold induced disorders (e.g.
necrotising enterocolitis, pulmonary fibrosis, exfoliative dermatitis, bone marrow
aplasia or other sever hematologic disorders), porphyria; History of severe allergic
or anaphylactic reactions or hypersensitivity to auranofin or other gold compounds.

- Treatment with nucleoside/nucleotide analogs with higher risk of mitochondrial
toxicity: zidovudine (ZDV), Stavudine (d4T), didanosine (ddI), di-deoxy-cytidine
(ddC) or abacavir (ABC).

- Presence of clinically significant skin/mucosal disease such as hives or dermatitis,
pruritus or rash, eczema, stomatitis or conjunctivitis

- Significant acute medical illness in the past 4 weeks

- Inflammatory bowel disease, Crohn's disease or ulcerative colitis

- Current or recent (i.e. within 2 weeks) gastrointestinal disease or GI disturbances,
including vomiting, abdominal pain, diarrhea, which may impact the absorption of the
investigational drug

- History of gastrointestinal surgery that could impact upon the absorption of
Auranofin

- Scheduled elective surgery or other procedures requiring general anesthesia during
the study

- Participant has the following laboratory values within 2 weeks before starting the
investigational drug (laboratory tests may be repeated, as clinically indicated, to
obtain acceptable values before failure at screening is concluded)

- Known hepatitis B or C infection as indicated by the presence of Hepatitis B surface
antigen (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood

- Receipt of immunomodulating therapy, EPO or G-CSF, immunization or systemic
chemotherapeutic agents within 12 weeks prior to study entry

- Anticipated requirement for treatment with drugs that may interfere with auranofin as
outlined in Appendix 7.

- Receipt of RBC or platelet transfusion or receipt of cell product within 24 weeks
prior to study entry

- Insulin dependent diabetes

- Systemic Lupus Erythematosus (SLE)

- Current or history of seizure disorder

- Previous diagnosis of lymphoma or other HIV related cancers.

- Any other significant disease or disorder (including psychiatric disorders) which, in
the opinion of the Investigator, may either put the participants at risk because of
participation in the study, or may influence the result of the study, or the
participant's ability to participate in the study.

- Women who are pregnant or breastfeeding, or with a positive pregnancy test during
screening or Women of Child Bearing Potential (WOCBP) who are unwilling or unable to
use an acceptable method of contraception to avoid pregnancy for the entire study
period and for at least 4 weeks before and 24 weeks after study treatment

- Males or females who are unwilling or unable to use barrier contraception during
sexual intercourse for the entire study period, including at least 4 weeks before, 4
weeks after study treatment, and when plasma HIV-RNA is detectable using standard
assays

- Subjects who have participated in another research study involving an investigational
product in the past 12 weeks.