MARCH Vascular Endothelium Substudy

Study Overview
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Brief Summary
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This is a substudy of MARCH, in which we are exploring the changes in the vascular endothelium using pulse wave tonometry (a non invasive measure of cardiac health) to measure the changes in small and large arterial elasticity in participants of the MARCH study who switch to maraviroc-based regimens over 96 weeks of follow-up.

Detailed Description
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Cardiovascular disease is increasingly recognised as a complication of HIV +/- therapies to treat it. Blood vessel elasticity, or compliance, can be depicted as the ability of the vessels to convert intermittent blood flow (cardiac ejection during systole) to continuous blood flow throughout the cardiac cycle. The compliance, or ability of vessels to accept energy, can be subdivided into elasticity of large and small vessels. Pulse wave tonometry is a non-invasive technique performed using a hand-held tonometer that generates two indices which correspond to large artery elasticity (LAE) and small artery elasticity (SAE). LAE and SAE estimates by pulse waveform analysis have previously shown greater correlation to Framingham risk when directly compared with other techniques such as flow-mediated diltation, and both LAE and SAE are associated with traditional cardiovascular risk factors (smoking, insulin resistance, hypertension). It is unclear what the net effect of maraviroc, a chemokine-receptor blocker is on cardiovascular function. The aims of this substudy are: To compare changes in the vascular endothelium between the control arm ((N(t)RTI) plus PI/r) and each of the maraviroc switch arms over 48 weeks of follow-up. To compare the changes in biomarkers and selected immunological markers between the control arm ((N(t)RTI) plus PI/r) and each of the maraviroc switch arms over 48 weeks of follow-up.

Official Title
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Maraviroc Switch Vascular Endothelium (VE) Substudy: a Substudy of MARCH

Conditions
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Cardiovascular Disease

Intervention / Treatment
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* Drug: NRTI + PI
* Drug: maraviroc + PI
* Drug: maraviroc + NRTI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Enrolled prior to treatment in the parent study; Provision of written, informed consent for participation in the substudy Exclusion Criteria: Known supraventricular tachycardia such as atrial flutter and/or fibrillation that precludes the measurement of pulse wave using tonometry.

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Arm 1<br>NRTI and PI | Drug: NRTI + PI<br>* tenofovir zidovudine abacavir lamivudine emtricitabine ritonavir darunavir atazanavir lopinavir fosamprenavir<br>|
| Arm 2<br>Maraviroc + PI | Drug: maraviroc + PI<br>* maraviroc ritonavir darunavir atazanavir lopinavir fosamprenavir<br>|
| Arm 3<br>maraviroc + NRTI | Drug: maraviroc + NRTI<br>* maraviroc tenofovir zidovudine abacavir lamivudine emtricitabine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in small arterial elasticity (SAE) as measure by pulse wave tonometry | measured at 6 timepoints week 0, 4, 12, 24, 48, 96 | 96 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| • Mean change in large arterial elasticity (LAE) as measure by pulse wave tonometry | measured at 6 timepoints, week 0,4,12,24,48,96 | 96 weeks | 
| • Changes from baseline in selected soluble markers of immune activation, coagulation, vascular and platelet function | stored bloods from the main study will be used to explore changes in vascular biomarkers | 96 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cardiovascular function, maraviroc