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

Study Overview
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Brief Summary
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Potent HIV suppression with Darunavir-based antiretroviral therapy (ART) will lead to repopulation of gastrointestinal-associated lymphoid tissue (GALT) cluster of differentiation (CD)4+ T-cell populations, normalization of systemic immune activation, and improved HIV-associated cardiovascular disease (CVD) risk.

Detailed Description
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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.

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

Conditions
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Human Immunodeficiency Virus Infection

Intervention / Treatment
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* Drug: darunavir with ritonavir and fixed-dose viread+emtricitabine daily


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: HIV positive naive to ART<br>HIV subjects will receive open-label darunavir 800 mg in combination with ritonavir 100 mg tablets and fixed-dose combination viread + emtricitabine (Truvada®) to be taken once daily without regard to food. Subjects will undergo upper endoscopy, CT cardiac angiogram, intimal-medial thickening, and peripheral blood collection before and after 12 months of ART. | Drug: darunavir with ritonavir and fixed-dose viread+emtricitabine daily<br> <br> * Other names: darunavir (Prezista®) 800 mg with ritonavir 100 mg and Truvada® to be taken once daily;|
| No Intervention: normal control volunteers<br>HIV negative age-matched controls will undergo the same interventions and procedures without receiving ART at study entry and after 12 months. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of CD4+ T-cells in the Lamina Propria/mm2 Before and After 12 Months of Therapy Compared to Age-matched Control Volunteers Without HIV | CD4+ T-cells in the lamina propria/mm2 before and after 12 months of therapy compared to age-matched control volunteers without HIV. | Baseline, 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Percentage of Total Artery Diameter | computerized axial tomography angiography of the coronary arteries (CT-angio) before and after 12-months of Darunavir therapy | Baseline, 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, cardiovascular risk, systemic immune activation