Sevelamer for Reducing Endotoxemia and Immune Activation
Condition: HIV-1 Infection
MeSH terms: Endotoxemia
Intervention: Sevelamer carbonate; Sevelamer carbonate
Intervention description: Patients will be administered two 800 mg tablets of Sevelamer carbonate orally three times a day for 8 weeks.
Intervention MeSH terms: Sevelamer
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      HIV-infected people can have an increase in inflammation in their body organs, even after
      taking anti-HIV medicines.

      Sevelamer carbonate is used to bind phosphate in dialysis patients. It can also bind
      endotoxin in the gut and lowers endotoxin levels in the blood of dialysis patients. Sevelamer
      carbonate decreases the inflammation endotoxin causes in dialysis patients.

      A5296 is a phase II, single-arm study to evaluate the effect of 8 weeks of sevelamer
      carbonate administration on markers of microbial translocation and T-cell activation in the
      blood in chronically HIV-infected subjects not receiving ART.
    

Eligibility criteria:

        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.