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

NCT ID: NCT01766726

Last Updated: 2017-03-17

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 33 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2012-12-31
• Study Completion Date: 2016-01-31

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.

Conditions

HIV

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

No interventions assigned to this group

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.

No interventions assigned to this group

Eligibility Criteria

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

-men and women, ages 18+, without HIV infection

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:

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Steven K. Grinspoon, MD

Professor of Medicine, Harvard Medical School

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Steven K Grinspoon, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 33134423 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28945911 (View on PubMed)

Other Identifiers

2012P001138

Identifier Type: -

Identifier Source: org_study_id