A Double Blind Randomized Placebo Controlled Study Examining the Effects of a Non-Absorbable (Rifaximin) Antibiotic on the Chronic Immune Activation Observed In HIV-infected Subjects

Inclusion Criteria

- PARTICIPANT INCLUSION CRITERIA:

Patients who have agreed in the course of other research studies to have their records
reviewed will have the following elements evaluated from their existing records: age,
history of HIV infection, ART history and viral loads prior to informed consent, or else
these elements will be assessed after informed consent. All blood draws to assess
eligibility will be completed after obtaining informed consent. To participate in this
study the criteria listed below will need to be met.

1. Subjects must be 18 years of age or older.

2. Able and willing to provide written informed consent

3. Must have a history of documented HIV infection.

4. HIV infection if not previously documented at host institutions will need to be
documented by a plasma HIV RNA viral load, rapid HIV test or any other licensed ELISA
test and confirmed by another test using a different method such as a rapid HIV test,
Western Blot, HIV culture, HIV antigen, HIV pro-viral DNA at any time prior to study
entry.

5. ART treated subjects who are virologically suppressed for at least 3 years. To meet
this criteria all documented viral loads in the 3 years (1095 days) prior to the
screening visit must be below the lower limit of detection [LLD] using standard
assays (i..e < 50 copies/mL). In each of the three prior years a single blip [i.e.,
viral loads above the lower limit of detection LLD] may be included provided they
satisfy the following criteria: the blips are below 400 copies/mL, and the blip is
surrounded (i.e., the preceding and succeeding viral loads) by undetectable HIV-1 RNA
level measurements. That is all viral loads must be below LLD EXCEPT for up to one
blip' in any 12 month period.

6. A minimum of 2 HIV-1 RNA levels that are below the lower limit of detection using
standard assays will be required during the 12 month period prior to their screening
visit. As assay characteristics across the sites can vary, LLD for the assay (i.e. <
50 copies/mL) will be used to define whether or not a subject is suppressed. All
viral loads in the 12 months prior to randomization should be below the LLD, a single
blip [i.e., viral loads above the lower limit of detection LLD] in the 12 month prior
to randomization may be included provided they satisfy the following criteria: the
blips are below 400 copies/mL, and the blip is surrounded (i.e., the preceding and
succeeding viral loads) by undetectable HIV-1 RNA level measurements.

7. Stable dose of statin therapy for 6 months if receiving statin therapy.

8. No known allergy or contraindication to the use of rifamycin compounds such as
rifampin, rifabutin or rifaximin..

9. The effect of rifaximin on the developing human fetus are unknown, therefore subjects
must be willing to use two methods of contraception (one of which must be a barrier
method) during the study period. Adequate methods of birth control include: tubal
ligation, hysterectomy, condoms (male or female) with or without a spermicide;
diaphragm or cervical cap with spermicide; intrauterine device; any of the methods
that require a prescription (such as contraceptive pills or patch, Norplant,
Depo-Provera, and others) or a male partner who has previously undergone a vasectomy.

THE FOLLOWING ELEMENTS WILL BE ASSESSED WITH A BLOOD DRAW AND AFTER OBTAINING INFORMED
CONSENT.

1. Detectable low-level viremia (0.6 copies/mL or greater) by the single copy assay but
< 50 copies/mL

2. Absolute Neutrophil count (ANC) x750/mm(3)

3. Hemoglobin greater than or equal to 11.0 g/dL

4. Platelet count greater than or equal to 75,000/mm(3)

5. Estimated Glomerular Filtration Rate (eGFR) > 60 mL/min, eGFR will be calculated
using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation

6. Confirmed serum glutamate pyruvate transaminase (SGPT) /serum glutamate oxaloacetate
transferase (SGOT) < 3times the upper limit of normal (ULN)

7. INR< the ULN for the assay

8. Negative urine pregnancy test at randomization

9. No evidence of active hepatitis B or hepatitis C (active hepatitis B will be defined
as a positive hepatitis B surface antigen present on a single determination, whereas
a positive result on hepatitis C RNA will be considered as evidence of active
hepatitis C)

All of the above laboratory testing will be completed in the 70 days prior to
randomization.

PARTICIPANT EXCLUSION CRITERIA:

1. Known bleeding diathesis (for example a diagnosis of hemophilia or Von Willebrand
disease)

2. Active drug use or alcohol abuse/dependence, which in the opinion of the
investigators will interfere with the patient's ability to participate in the study

3. Serious illness requiring systemic treatment and/or hospitalization within 30 days of
screening into the study

4. Evidence of active opportunistic infections or neoplasms (excluding cutaneous basal
cell carcinoma and squamous cell carcinoma) in the 6 months prior to randomization

5. History of inflammatory bowel disease (Crohn's Disease, ulcerative colitis)

6. Positive urine pregnancy test at screening

7. Breastfeeding

8. Current imprisonment

9. Concurrent immunomodulatory agents, including systemic corticosteroids in the 12
weeks prior to randomization. Topical, nasal or inhaled corticosteroid use is allowed

10. Concomitant use of probiotics except yogurt

11. Chronic antibiotic use such as tetracyclines for acne

12. Vaccinations within 6 weeks of randomization

13. Concomitant use of warfarin, clopidogrel, or heparin

14. Child-Pugh Class C disease

15. A prior history of Clostridium difficile colitis

16. Any condition that precludes the safe administration of conscious sedation for
endoscopy (such as decompensated lung or heart disease) will not be able to
participate in the colonoscopy aspect of the protocol.