Sevelamer Carbonate for Reducing Endotoxemia and Immune Activation: A Proof of Concept Study

Inclusion Criteria:

- HIV-1 infection

- No plans to initiate ART during the course of the proposed study.

- Screening CD4+ T-cell count ≥ 400 cells/mm3 performed in a laboratory that has a
Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent.

- HIV-1 RNA >50 copies/mL within the last 180 days prior to entry.

- Screening serum phosphate > 2.6 mg/dL within 60 days prior to entry.

- Certain laboratory values, as detailed in section 4.1.6 of the protocol, obtained
within 30 days prior to entry

- Female subjects of reproductive potential must have a negative serum or urine
pregnancy test performed within 30 days prior to entry.

- Female subjects participating in sexual activity that could lead to pregnancy must
agree to use at least one of the following forms of birth control for at least 30
days prior to study entry until the final study visit:

- Condoms (male or female) with or without a spermicidal agent

- Diaphragm or cervical cap with spermicide

- Intrauterine device (IUD)

- Hormone-based contraceptive

- Female subjects who are not of reproductive potential are eligible without requiring
the use of a contraceptive.

- Confirmation of the availability of the stored pre-entry plasma and peripheral blood
mononuclear cell (PBMC) samples for endotoxin, sCD14, and immune activation
determinations, obtained from a fasting sample.

- Ability and willingness of subject to provide informed consent.

- No plans to use probiotics (defined as products that contain significant amounts of
live microorganisms and are ingested for specific health benefits, e.g., yogurt with
live and active cultures, Lactobacillus GG, Saccharomyces boulardii) during the
study.

Exclusion Criteria:

- Known diagnosis of acute HIV infection within 180 days prior to study entry.

- Pregnant or breastfeeding.

- Use of any antiretroviral agent within 24 weeks prior to study entry.

- Use of systemic cancer chemotherapy or radiation therapy, immunosuppressive or
immunomodulatory therapy (e.g., interferons, tumor necrosis factor antagonists,
interleukins, systemic corticosteroids) within 24 weeks prior to study entry.

NOTE A: Use of inhaled steroids, nasal steroids, topical steroids, or the equivalent of 10
mg of prednisone or less per day or a less than 2-week course of oral steroids is not
exclusionary.

NOTE B: A single course of 1% hydrocortisone cream applied up to 3 times a day to <10
square inches area for <2 weeks is permitted while on study. Use of all other topical
steroids is excluded.

- Known allergy/sensitivity or any hypersensitivity to components of the study drug or
its formulation.

- Active drug or alcohol use or dependence that, in the opinion of the site
investigator, would interfere with adherence to study requirements.

- Serious illness requiring systemic treatment and/or hospitalization within 60 days
prior to study entry.

- Known cirrhosis or severe liver disease (e.g., ascites, encephalopathy, history of
variceal bleeding).

NOTE: Potential subjects with chronic hepatitis B or C virus infection who do not have
known cirrhosis or severe liver disease may participate in the study.

- Severe kidney disease (defined as estimated glomerular filtration rate [GFR] <30
mL/min/1.73m2) at screening.

- History of bowel obstruction or severe GI motility disorders including severe
constipation.

- Severe dysphagia or swallowing disorders.

- Major GI tract surgery within 60 days prior to study entry.

- Intent to initiate or change the dose of lipid-lowering drugs during study. NOTE:
Potential subjects on stable doses of lipid-lowering agents (defined as no change in
preparation or dose within 90 days prior to study entry) are permitted and may be
enrolled.

- Use of investigational therapies within 90 days prior to study entry unless
permission was granted by the A5296 protocol chairs (see Study Management page).

- Currently receiving hepatitis C therapy or anticipation that such therapy will be
started during the study.

- Use of probiotics, for more than 3 consecutive days within the 60 days prior to study
entry.