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

March 15, 2017 updated by: Steven K. Grinspoon, MD, Massachusetts General Hospital
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.

Study Overview

Status

Completed

Conditions

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 Type

Observational

Enrollment (Actual)

33

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

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.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Aortic/coronary target to background ratio (TBR) on cardiac FDG-PET
Time Frame: 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).
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)
Time Frame: Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild
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
Time Frame: 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.
Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild
Indices of pro-atherogenic lipid dysfunction
Time Frame: 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.
Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild
Inflammatory biomarker levels
Time Frame: 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.
Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild
Percentage of circulating activated leukocyte subsets
Time Frame: 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.
Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Massachusetts General Hospital

Collaborators

Gilead Sciences

Investigators

  • Principal Investigator: Steven K Grinspoon, MD, Massachusetts General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2012

Primary Completion (Actual)

January 1, 2016

Study Completion (Actual)

January 1, 2016

Study Registration Dates

First Submitted

January 9, 2013

First Submitted That Met QC Criteria

January 9, 2013

First Posted (Estimate)

January 11, 2013

Study Record Updates

Last Update Posted (Actual)

March 17, 2017

Last Update Submitted That Met QC Criteria

March 15, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2012P001138

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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