Mechanisms of Immune Reconstitution & Reduced Immune Activation Following Darunavir-based ART

Rationale Infection with HIV causes significant morbidity and mortality, even among
individuals who are virologically suppressed with combination anti-retroviral therapy (ART).
ART is effective in prolonging life and enabling individuals who are HIV positive to live
near-normal life spans. However, these individuals are increasingly developing a number of
chronic diseases of aging, such as atherosclerotic cardiovascular disease (ASCVD). The
proposed studies will examine the role of highly active antiretroviral therapy in restoring
the mucosal immunity and the systemic effect on immune activation, bacterial translocation,
and change in HIV-associated cardiovascular disease risk.

Inclusion Criteria:

- Willing to sign consent form

- Naïve to ART (remote ART use >5 years will be considered on a case by case basis)

- No known GI or cardiovascular disease

- Between the ages of 18 and 60

- No active opportunistic infections or therapy for acute OI within 30 days of entry.
Subjects can be on secondary prophylaxis with a history of AIDS defining illness.

- All women of childbearing potential (WCBP) must have a negative urine pregnancy test
before any of the invasive or radiation exposure study procedures.

- Normal population should be free of chronic metabolic conditions such as diabetes,
hypercholesterolemia, or coronary artery disease

- There are no CD4+ T-cell count or HIV plasma viral load restrictions.

Exclusion Criteria:

- Abnormal coagulation parameters (PT>1.2 upper limit of normal (ULN))

- Thrombocytopenia (platelet count <50.000 within 6 weeks)

- Contra-indications to upper endoscopy or conscious sedation

- Anemia (>grade 1 [appendix 1])

- Aspirin, ibuprofen, warfarin or other agents that interfere with the coagulation
cascade are prohibited within 1 week of endoscopy.

- Renal insufficiency (serum Creatinine >1.2 ULN)

- History of chronic proteinuria that could impact viread use.

- Allergy to contrast used for CT angiography

- Requirement to take medications that are contraindicated with study ART regimen.