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

NCT01766726 | Completed

• 1 other identifier: 2012P001138
• Study Type: observational
• Target: 33
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV

Keywords

HIV; Atherosclerosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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

• Lipid and lipoprotein levels

  Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild

• Indices of pro-atherogenic lipid dysfunction

  Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild

• Inflammatory biomarker levels

  Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild

• Percentage of circulating activated leukocyte subsets

  Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild

Study Arms (2)

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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:
• men and women, ages 18+, without HIV infection

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Gilead Sciences: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (2)

• 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.

  PMID: 33134423 DERIVED

• 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.

  PMID: 28945911 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma, serum.

MeSH Terms

Conditions

Atherosclerosis

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Steven K Grinspoon, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine, Harvard Medical School

Study Record Dates

• First Submitted: January 9, 2013
• First Posted: January 11, 2013
• Study Start: December 1, 2012
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: March 17, 2017

Record last verified: 2017-03

Locations

US (1)