A Study of the Gut Barrier and Blood Vessel Inflammation in Individuals With and Without HIV

As more people with HIV gain access to combination antiretroviral therapy (cART),
cardiovascular disease has become increasingly prevalent and a significant cause of
mortality. Activation of the innate immune system may stimulate inflammatory mechanisms of
atherosclerosis development. Loss of gastrointestinal (GI) mucosal epithelial integrity and
loss of CD4+ T-lymphocytes in the intestinal lamina propria occur in HIV-infected patients
and are not fully restored by cART. Translocation of microbial products from the intestinal
lumen into the systemic circulation has been demonstrated to be increased in HIV-infected
patients and the investigators hypothesize that it is a key driver of monocyte and
macrophage activation. In turn, these pro-inflammatory monocytes and macrophages can induce
atherosclerotic disease development. The purpose of the research study is to determine the
effects of a glucagon-like peptide-2 analog, teduglutide, on intestinal epithelial
integrity, microbial translocation across the gut lumen, markers of innate immune system
activation including the monocyte transcriptome, bone, arterial inflammation, and
atherosclerosis in a 6-month randomized, double-blind placebo-controlled proof of concept
trial in HIV-infected individuals.

Inclusion Criteria:

1. Men and women age 21-60 with previously diagnosed HIV disease

2. Stable anti-retroviral therapy (ART) as defined by no changes in ART regimen for >6
months

3. To be eligible for colonoscopy procedure, laboratory values that meet the following
criteria:

1. Hemoglobin > 9.0 g/dL

2. Absolute neutrophil count ≥ 1000/mm3

3. Platelet count ≥ 100,000/mm3

4. Prothrombin time (PT) < 1.2 x upper limit of normal (ULN)

5. Partial thromboplastin time (PTT) < 1.5 x ULN

4. Ability and willingness to give written informed consent and to comply with study
requirements

Exclusion Criteria:

1. History of clinically significant gastrointestinal disease including but not limited
to: colon cancer, intestinal obstruction, ulcerative colitis, Crohn's disease, or
history of C. difficile within the past 3 months

2. Active gall bladder, biliary or pancreatic disease

3. Female subject who is pregnant, nursing or less than 8 weeks post partum.

4. Use of any immunomodulatory agents within 30 days prior to study enrollment

5. History of intolerance, sensitivity, allergy or anaphylaxis to benzodiazepines or
other narcotics to be used during the colonoscopy procedure

6. Contraindication to beta-blocker (including moderate to severe asthma or heart block)
or nitroglycerin use as these drugs are given as part of the standard cardiac CT
protocol. Previous allergic reaction to beta blocker or nitroglycerin.

7. Patients with previous allergic reactions to iodine-containing contrast media

8. Renal disease or creatinine >1.5 mg/dL (contrast will be administered during CT
angiography of the heart)

9. History of requiring antibiotic prophylaxis for invasive procedures

10. History of myocardial infarction, decompensated cirrhosis, or any other condition
that in the opinion of the investigator will compromise ability to participate in the
study

11. Currently taking anticoagulants including but not limited to: heparin (Hep-Lock,
Hep-Pak), Hep-Pak CVC, Heparin Lock Flush), warfarin (Coumadin), tinzaparin
(Innohep), enoxaparin (Lovenox), danaparoid (Orgaran), dalteparin (Fragmin),
clopidogrel (Plavix), prophylactic aspirin, and regular NSAID use

12. Subject taking any of the following medications: statins, systemic steroids (inhaled
or nasal steroid therapy is permitted), interleukins, systemic interferons (e.g.
local injection of interferon alpha for treatment of HPV is permitted), systemic
chemotherapy including oral chemotherapeutic agents, methotrexate, octreotide, growth
hormone, antiarrhythmics including digoxin, antiepileptics, immunosuppressants,
vancomycin, rifampin, aminoglycosides, clonidine, prazosin, lithium and
ritonavir-boosted lopinavir (Kaletra).

13. Subject has had two or more endoscopy procedures (sigmoidoscopy, upper endoscopy or
colonoscopy) within the past 12 months for clinical purposes or other research
studies.

14. Body weight greater than 300 lbs due to CT scanner table limitations

15. Active illicit drug use

16. Patients who report any significant radiation exposure over the course of the year
prior to randomization. Significant exposure is defined as:

1. More than 2 percutaneous coronary interventions (PCI) within 12 months of
randomization

2. More than 2 myocardial perfusion studies within the past 12 months

3. More than 2 CT angiograms within the past 12 months

4. Any subjects with history of radiation therapy

17. Patients already scheduled or being considered for a procedure or treatment requiring
significant radiation exposure (e.g., radiation therapy, PCI, or catheter ablation of
arrhythmia) within 12 months of randomization

18. History of malignancy

19. Prior recipient of a HIV vaccine