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| Name | Class |
|---|---|
| Gilead Sciences | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Healthy control subjects | 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 | 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. |
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| 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 |
| 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 |
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HIV-infected Subjects:
Inclusion Criteria:
Exclusion Criteria:
Healthy control subjects:
Inclusion Criteria:
-men and women, ages 18+, without HIV infection
Exclusion Criteria:
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Subjects with HIV infection being cared for in the Eastern Massachusetts area may be appprised of the study by their treating infectious disease doctors. Additionally, subjects with HIV infection from the community will be recruited via posters, advertisements, e-postings. Healthy control subjects from the community will be recruited via posters, advertisements, and e-postings.
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| Name | Affiliation | Role |
|---|---|---|
| Steven K Grinspoon, MD | Massachusetts General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33134423 | Derived | Toribio M, Burdo TH, Fulda ES, Cetlin M, Chu SM, Feldpausch MN, Robbins GK, Neilan TG, Melbourne K, Grinspoon SK, Zanni MV. Effects of Integrase Inhibitor-Based ART on the NLRP3 Inflammasome Among ART-Naive People With HIV. Open Forum Infect Dis. 2020 Sep 29;7(10):ofaa459. doi: 10.1093/ofid/ofaa459. eCollection 2020 Oct. | |
| 28945911 |
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| ID | Term |
|---|---|
| D050197 | Atherosclerosis |
| ID | Term |
|---|---|
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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Plasma, serum.
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 |
| Toribio M, Park MH, Zanni MV, Robbins GK, Burdo TH, Williams KC, Feldpausch MN, Stone L, Melbourne K, Grinspoon SK, Fitzgerald ML. HDL Cholesterol Efflux Capacity in Newly Diagnosed HIV and Effects of Antiretroviral Therapy. J Clin Endocrinol Metab. 2017 Nov 1;102(11):4250-4259. doi: 10.1210/jc.2017-01334. |