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

HIV Clinical Trial

— Quad  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01766726
• Other study ID #: 2012P001138
• Status: Completed
• Phase: N/A
• First received: January 9, 2013
• Last updated: March 15, 2017
• Start date: December 2012
• Est. completion date: January 2016

Study information

• Verified date: March 2017
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: January 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• HIV
• Inflammation

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	Gilead Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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