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

Completed

• Conditions: HIV

• Registration Number: NCT01766726
• Lead Sponsor: Massachusetts General Hospital

Brief Summary

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

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.

Study Timeline

• Study Start: 2012-12
• Study First Submitted: 2013-01-09
• Study First Submitted QC: 2013-01-09
• Study First Posted: 2013-01-11
• Primary Completion: 2016-01
• Study Completion: 2016-01
• Status Verified: 2017-03
• Last Update Submitted: 2017-03-15
• Last Update Posted: 2017-03-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 33

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States