Efficacy of Maraviroc in Modulating Atherosclerosis in HIV Patients.

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Efficacy of Maraviroc in Modulating Atherosclerosis in HIV Patients.

Conditions
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HIV Infection With Other Conditions, Cardiovascular Risk Factor, Atherosclerosis, Inflammation

Intervention / Treatment
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* Drug: Maraviroc 300 mg


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>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<br>* 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.<br>|
| Experimental: B<br>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<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Maraviroc, Atherosclerosis