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

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $829,709

## Abstract

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.

## Key facts

- **NIH application ID:** 9927415
- **Project number:** 1R01HL149516-01A1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Janet Lo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $829,709
- **Award type:** 1
- **Project period:** 2020-09-05 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9927415

## Citation

> US National Institutes of Health, RePORTER application 9927415, Reducing Arterial Inflammation and Improving Metabolic Health by Dual CCR2 and CCR5 Antagonism in People Living with HIV (1R01HL149516-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9927415. Licensed CC0.

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