Clinical trial NCT01766726: Effects of Newly-Initiated QUAD Therapy on Aortic/Coronary Inflammation in ART-Naïve Infected Patients
Official title: Effects of Newly-Initiated QUAD Therapy on Aortic/Coronary Inflammation in ART-Naïve Infected Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV
Keywords: HIV
Atherosclerosis
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
First posted: 2013-01-11
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Aortic/coronary target to background ratio (TBR) on cardiac FDG-PET
timeFrame: Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild
Secondary outcomes:
measure: Aortic/coronary atherosclerotic plaque on coronary computed tomography angiography (coronary CTA)
timeFrame: Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild
measure: Lipid and lipoprotein levels
timeFrame: Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild
measure: Indices of pro-atherogenic lipid dysfunction
timeFrame: Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild
measure: Inflammatory biomarker levels
timeFrame: Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild
measure: Percentage of circulating activated leukocyte subsets
timeFrame: Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Steven K Grinspoon, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.