Efficacy of Maraviroc in Modulating Atherosclerosis in HIV Patients.

The investigator tested the efficacy of maraviroc intensification on down-regulating atherosclerotic progression in HIV infected patients with optimal viro-immunologic control and at high cardiovascular risk.

Study Overview

• Status: Completed
• Conditions: Inflammation; Atherosclerosis; Cardiovascular Risk Factor; HIV Infection With Other Conditions
• Intervention / Treatment: Drug: Maraviroc 300 mg

Detailed Description

Experimental CCR5 antagonism with maraviroc in atherosclerosis-prone mice and preliminary data in humans suggest an anti-atherosclerotic effect of the drug. The investigators assessed the impact of maraviroc treatment in HIV-infected patients on several subclinical indicators of atherosclerosis and putative mechanisms for such an effect.

HIV-treated patients under effective antiretroviral (ART) therapy, with a Framingham risk score >20% and a brachial flow-mediated dilation (bFMD) <4%, as indices of high cardiovascular risk, were recruited. Maraviroc (300 mg per os for 24 weeks) was administered on top of ART to all participants using a cross-over design. Brachial FMD, carotid-femoral pulse wave velocity (cfPWV) and carotid intima-media thickness (cIMT) were measured as non-invasive markers of atherosclerosis. Vascular competence, as expressed by the ratio of circulating endothelial micro-particles (EMPs) to endothelial progenitor cells (EPCs), as well as markers of systemic inflammation, monocyte activation and platelet activation were assessed.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Perugia, Italy, 06126
    • Elisabetta Schiaroli

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Eligible patients were consecutive ≥50-year-old individuals, treated for over 1 year with an effective protease inhibitor ART regimen (HIV RNA <50 copies/mL), with CD4 T cell counts > 300/ mm3 for at least 6 months and a Framingham risk score >20% and bFMD <4%.

Exclusion Criteria:

• Patients over 70 years of age, with life expectancy < 12 months, with known platelets functional defects or alcohol chronic abuse were excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: A; Patients received Maraviroc 300 mg/day in addition to current ART for 24 weeks. At the end of the first 24-week period patients were switched to ART with no additional treatment.	Drug: Maraviroc 300 mg; Patients were randomly allocated with an AB/BA cross over design to either maraviroc 300 mg/day to current ART for 24 weeks (A) or no additional treatment (B). At the end of the first 24-week period patients were switched to the alternative arm.
EXPERIMENTAL: B; Patients received ART with no additional treatment for 24 weeks. At the end of the first 24-week period patients were switched to Maraviroc 300 mg/day in addition to current ART.	Drug: Maraviroc 300 mg; Patients were randomly allocated with an AB/BA cross over design to either maraviroc 300 mg/day to current ART for 24 weeks (A) or no additional treatment (B). At the end of the first 24-week period patients were switched to the alternative arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change Flow Mediated Dilation	24 weeks
Change in Intima-Media Thickness	24 weeks
Change in carotid-femoral Pulse Wave Velocity	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in inflammatory markers	change in CRP, IL6, D-dimer	24 weeks
Endothelial microparticles/endothelial progenitor cells ratio		24 weeks

Collaborators and Investigators

• Sponsor: University Of Perugia

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2015
• Primary Completion (ACTUAL): April 30, 2017
• Study Completion (ACTUAL): September 30, 2017

Study Registration Dates

• First Submitted: January 10, 2018
• First Submitted That Met QC Criteria: January 10, 2018
• First Posted (ACTUAL): January 18, 2018

Study Record Updates

• Last Update Posted (ACTUAL): January 23, 2018
• Last Update Submitted That Met QC Criteria: January 19, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: HIV; Atherosclerosis; Maraviroc
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Inflammation; Atherosclerosis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; CCR5 Receptor Antagonists; Maraviroc
• Other Study ID Numbers: UPerugia03

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No