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Reducing Arterial Inflammation and Improving Metabolic Health by Dual CCR2 and CCR5 Antagonism in People Living with HIV

Award Number: R01HL149516
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY/ ABSTRACT People living with HIV infection have increased risk of cardiovascular disease (CVD), despite effective antiretroviral therapy. Emerging evidence show that residual persistent immune dysregulation contributes to CVD risk in the HIV population. In addition, metabolic disorders including insulin resistance, dyslipidemia and increased visceral adiposity are common in people with HIV and also contribute significantly to excess CVD risk. The key hypothesis of this grant application is that CCR2 and CCR5 drive inflammatory macrophages and T- cells into tissues including arterial intima causing atherosclerosis, and into adipose tissue causing insulin resistance. We expect that dual antagonism of CCR2 and CCR5 chemokine receptors will reduce immune activation, reduce inflammation in the vasculature, reduce adipose tissue inflammation and reduce insulin resistance. To test our hypotheses, we propose a multicenter placebo-controlled, double-blind, 24-week long, randomized trial of cenicriviroc vs. placebo (in 2:1 ratio) in 93 adult men and women living with HIV with suppressed HIV-1 RNA on stable ART who have increased CVD risk to 1) determine the impact of dual CCR2/CCR5 antagonism with cenicriviroc on arterial inflammation and circulating soluble and cellular markers of inflammation and immune activation and 2) To determine the impact of dual CCR2/CCR5 antagonism with CVC on insulin resistance and adipose tissue inflammation, gene expression, and immune cells. This proposal will leverage the clinical trial infrastructure of the ACTG and the extensive scientific expertise of collaborating investigators and laboratories within the ACTG.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2022 ( Subtotal = $771,996 )
2022	2022	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cardiovascular Diseases Research	001	3	8/25/2022	NON-COMPETING CONTINUATION	$771,996
2022	2021	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cardiovascular Diseases Research	000	2	2/1/2022	NON-COMPETING CONTINUATION	$0


Issue Date FY: 2021 ( Subtotal = $778,106 )
2021	2021	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cardiovascular Diseases Research	000	2	8/25/2021	NON-COMPETING CONTINUATION	$778,106


Issue Date FY: 2020 ( Subtotal = $829,709 )
2020	2020	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cardiovascular Diseases Research	000	1	9/3/2020	NEW	$829,709


Grand Total All Awards = $2,379,811

Sum of Action Amount is $2,379,811;

Grand Total = $2,379,811

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Reducing Arterial Inflammation and Improving Metabolic Health by Dual CCR2 and CCR5 Antagonism in People Living with HIV

Award Number: R01HL149516

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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