Maraviroc Abacavir STudy - Effect on Endothelial Recovery

Study Overview
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Brief Summary
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HIV infected patients treated with abacavir might have a higher risk for the occurrence of cardiovascular events. At time of writing of this protocol the underlying mechanism is not yet elucidated, however some studies find impaired endothelial function and elevated markers of chronic inflammation in these patients,suggesting a higher lever of chronic inflammation. Recently maraviroc (Celsentri®), a CCR5-receptor antagonist, became available for treatment of patients infected with HIV-1. Improvement of endothelial function may be a potential beneficial side effect of treatment with maraviroc, due to the potential reduction of immune activation and chronic inflammation as a result of blocking the CCR5-coreceptor. Moreover, treatment intensification of HAART with maraviroc in patients with suppressed plasma HIV_RNA may decrease plasma HIVRNA below the cut-off of 50 copies/ml as well. The investigators hypothesize that maraviroc intensification therapy in patients on an abacavir-containing regimen will improve endothelial function. The objectives of this study are: First, to assess the effect of addition of maraviroc to an abacavir-containing regimen on endothelial function; second, to assess the effect of this intervention on markers of immune activation and chronic inflammation, and on plasma HIV-RNA below 50 copies/ml.

Detailed Description
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The MASTER study is a phase IV, randomized, open label, cross-over, intervention study. Study subjects who are on stable abacavir-containing regimen will be randomized into two arms. In arm A maraviroc will be added to their regimen at baseline, while study subjects in arm B will continue their abacavir-containing regimen. After 8 weeks, cross-over of the study arms will be performed. Subjects in arm A will then stop maraviroc, while in subjects in arm B maraviroc will be added to their regimen (for 8 weeks again). The total duration of the study will be 16 weeks.

Official Title
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Maraviroc Abacavir STudy - Effect on Endothelial Recovery

Conditions
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Endothelial Dysfunction

Intervention / Treatment
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* Drug: Maraviroc


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years HIV-1 infection Treatment with antiretroviral regimen containing abacavir for at least the previous 3 months Undetectable plasma HIV RNA (50 cp/ml) for at least 6 months (one 'blip' allowed, which is defined as a detectable plasma HIV-RNA level between 50 and 400 copies/ml, preceded and followed by undetectable (<50 copies/ml) plasma HIV-RNA measurements) CD4+ cell count > 200 cells/μL Signed informed consent Exclusion Criteria: Pregnancy Breastfeeding Allergy for peanuts or soya Hypersensitivity for maraviroc Treatment of underlying malignancy Acute infection in the preceding 30 days Renal insufficiency requiring hemodialysis Acute or decompensated chronic hepatitis Modification of antiretroviral regimen in the previous 3 months

Ages Eligible for Study
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Minimum Age: 18 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A<br>HAART of subjects in arm A will be intensified with maraviroc during week 1-8. | Drug: Maraviroc<br>* HAART of subjects enrolled in arm A will be intensified with maraviroc during week 1-8.<br>* Other names: Celsentri;|
| Active Comparator: Arm B<br>HAART of subjects enrolled in arm B will be intensified with maraviroc during week 9-16 | Drug: Maraviroc<br>* HAART of subjects enrolled in arm A will be intensified with maraviroc during week 1-8.<br>* Other names: Celsentri;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in flow-mediated dilatation (FMD) of the brachial artery after 8 weeks of maraviroc treatment as compared to the control group |  | After 8 weeks of treatment (cross-over) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in markers of chronic inflammation |  | Baseline, week 2, week 4, week 8, week 10, week 12 and week 16 | 
| Change in markers of immune activation |  | Baseline, week 2, week 4, week 8, week 10, week 12 and week 16 | 
| Change in markers of endothelial function |  | Baseline, week 2, week 4, week 8, week 10, week 12 and week 16 | 
| Changes in plasma HIV-RNA below 50 copies/ml |  | Baseline, week 8, week 16 | 
| Change in endothelial function measured by EndoPAT |  | baseline, week 8, week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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endothelial function, CCR5 receptor, Maraviroc, Abacavir, Flow Mediated Dilatation, EndoPAT