Effects of Newly-Initiated QUAD Therapy on Aortic/Coronary Inflammation in ART-Naïve Infected Patients

Study Overview
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Brief Summary
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The main aims of this study are to determine whether: a) ART-naïve HIV+ subjects have increased artherosclerotic plaque inflammation/vulnerability, b) newly-initiated QUAD/Stribild therapy will decrease plaque inflammation/vulnerability in these subjects, and c) QUAD/Stribild therapy will improve indices of immune dysregulation and lipid dysfunction as a mechanism of improved plaque inflammation/vulnerability. Parameters of lipid and immune function will also be assessed in healthy control subjects, for comparison.

Detailed Description
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Patients with HIV are at higher risk of morbidity and mortality from cardiovascular disease than healthy subjects. Antiretroviral therapy (ART) has greatly increased the lifespan of HIV+ patients, but their risk of CVD remains higher than normal. Previously, it has been shown that compared to healthy control subjects, ART-treated HIV+ patients have more atherosclerotic plaque inflammation in the aorta. This study is intended to determine whether atherosclerotic plaque inflammation/vulnerability is increased in ART-naïve HIV+ patients and whether these parameters can be improved through 6 months of newly-initiated QUAD/Stribild therapy. Additionally, the study will determine whether indices of immune dysregulation and lipid dysfunction are increased in ART-naive HIV+ patients and whether these parameters can also be improved through 6 months of newly initiated QUAD/Stribild therapy.

Official Title
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Effects of Newly-Initiated QUAD Therapy on Aortic/Coronary Inflammation in ART-Naïve Infected Patients

Conditions
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HIV

Participation Criteria
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Eligibility Criteria
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HIV-infected Subjects: Inclusion Criteria: men and women, ages 18+, with documented HIV-infection who are ART-naive and ready to be started on ART with QUAD/Stribild by their treating infectious disease doctors Exclusion Criteria: history of prior, sustained ART use CD4 <50 or AIDS-defining illness known current opportunistic infection or acute infections (not including Hepatitis B/C) pregnancy or breastfeeding history of acute coronary syndrome or coronary artery stenting or surgery, diabetes mellitus, or significant autoimmune/inflammatory disease plans for sustained use during 6 month study interval of a confounding immune suppressant medication including intravenous or oral corticosteroid hemoglobin < 12.5 g/dl for men or < 12 g/dl for women eGFR < 70 ml/min/1.73 m2 calculated by CDK-EPI contrast dye allergy contraindication to beta blockers or nitroglycerin administered during MDCT coronary angiography (coronary CTA) protocol body weight > 320 lbs (PET scanner limitation) significant radiation exposure (>2 myocardial perfusion scans or CT angiograms) received within the past year reported active illicit drug use Healthy control subjects: Inclusion Criteria: -men and women, ages 18+, without HIV infection Exclusion Criteria: known current opportunistic infection or acute infections (not including Hepatitis B/C) pregnancy or breastfeeding history of acute coronary syndrome or coronary artery stenting or surgery, diabetes mellitus, or significant autoimmune/inflammatory disease sustained use of a confounding immune suppressant medication including intravenous or oral corticosteroid hemoglobin < 12.5 g/dl for men or < 12 g/dl for women reported active illicit drug use

Ages Eligible for Study
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Minimum Age: 18 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy control subjects<br>Historical healthy control subjects matched to HIV+ patients on traditional cardiovascular risk factors will be studied at baseline with respect to arterial inflammation and coronary atherosclerotic plaque. Prospectively recruited healthy control subjects matched to HIV+ patients on traditional cardiovascular risk factors will be studied at baseline with respect to lipid and immune function. | |
| ART-naïve HIV+ patients starting QUAD/Stribild<br>ART-naïve HIV+ patients who are about to be started QUAD/Stribild by their treating clinicians will be studied at baseline and 6 months after initiating QUAD/Stribild therapy. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aortic/coronary target to background ratio (TBR) on cardiac FDG-PET | Degree of aortic/coronary atherosclerotic plaque inflammation assessed via cardiac FDG-PET as target to background ratio (TBR) of the standardized uptake value (SUV). | Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aortic/coronary atherosclerotic plaque on coronary computed tomography angiography (coronary CTA) | Aortic/coronary atherosclerotic plaque assessed via coronary CTA. | Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild | 
| Lipid and lipoprotein levels | Levels of lipids and lipoproteins including but not limited to levels of total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, and levels select apolipoprotein levels. | Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild | 
| Indices of pro-atherogenic lipid dysfunction | Including HDL oxidative potential and other assessments of HDL function and structure. | Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild | 
| Inflammatory biomarker levels | Levels of inflammatory biomarkers including but not limited to soluble CD163. | Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild | 
| Percentage of circulating activated leukocyte subsets | Percentage of circulating activated leukocyte subsets including but not limited to percentage of circulating CD14+CD16+ monocytes assessed via flow cytometry. | Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Atherosclerosis