Switch to Atazanavir and Brachial Artery Reactivity (SABAR) Study

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the change in brachial artery reactivity in HIV-infected subjects with elevated lipid levels who are switched to an atazanavir containing antiretroviral regimen

Detailed Description
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HIV-infected subjects on a stable protease inhibitor (PI) containing antiretroviral regimen with plasma HIV RNA <500 copies/mL, who have LDL cholesterol levels >130 mg/dL or fasting triglycerides levels >200 mg/dL, will be randomized (1:1) to continue their current antiretroviral regimen or to switch the PI to atazanavir (ATV). Brachial artery reactivity will be measured before (at entry) and 12 and 24 weeks after subjects are randomized. ARM A: Switch current PI to atazanavir 400 mg once daily plus current > 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) for 24 weeks. Subjects currently on ritonavir (RTV) (400 mg BID or greater) or RTV-boosted PI (<400 mg/day) , or tenofovir (TDF) as backbone NRTI therapy, will switch to ATV 300 mg boosted with RTV 100mg once daily. ARM B: Continue current antiretroviral regimen (single or RTV-boosted PI plus > 2 NRTIs) for 24 weeks Brachial artery reactivity in response to two vasoactive stimuli (increased forearm blood flow and nitroglycerin) will be assessed by measuring brachial artery diameter.

Official Title
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Switch to Atazanavir and Brachial Artery Reactivity (SABAR) Study: Endothelial Function in HIV-Infected Subjects Switched to an Atazanavir Regimen

Conditions
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HIV Infection, Hyperlipidemia

Intervention / Treatment
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* Drug: Atazanavir
* Drug: current antiretroviral regimen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV infection HIV-1 RNA < 500 copies/ml Fasting LDL cholesterol >130 mg/dl OR fasting triglycerides >200 mg/dl CD4 count >100 cells/mm Stable antiretroviral regimen for at least 12 weeks prior to study entry that includes a protease inhibitor (PI) with or without ritonavir boosting Exclusion Criteria: History of heart disease, uncontrolled hypertension, peripheral vascular disease Current non-nucleoside reverse transcriptase inhibitor (NNRTI) in the PI-containing regimen within 4 weeks Prior or current use of atazanavir Initiation of treatment with lipid-lowering drugs within 4 weeks prior to study entry

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>ARM A: Switch current PI to atazanavir 400 mg once daily plus current > 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) for 24 weeks. Subjects currently on ritonavir (RTV) (400 mg BID or greater) or RTV-boosted PI (<400 mg/day) , or tenofovir (TDF) as backbone NRTI therapy, will switch to ATV 300 mg boosted with RTV 100mg once daily. | Drug: Atazanavir<br>* atazanavir 400 mg once daily<br>* Other names: Reyataz;|
| Active Comparator: B<br>ARM B: Continue current antiretroviral regimen (single or RTV-boosted PI plus > 2 NRTIs) for 24 weeks | Drug: current antiretroviral regimen<br>* Continue current antiretroviral regimen for 24 weeks, single or RTV-boosted PI plus > 2 NRTIs<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change in Brachial Artery Flow Mediated (FMD) Vasodilation Between Arms From Baseline to Week 24 | Brachial artery reactivity assessed by noninvasively measuring brachial artery diameter and flow velocities in response to overinflated blood pressure cuff (Flow mediated dilation (FMD))in subjects switching to atazanavir and in subjects continuing on a stable antiretroviral regimen | Baseline to week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Total Cholesterol Levels From Baseline to Week 24 | Total cholesterol level changes within and between arms | Baseline to 24 weeks | 
| Changes in LDL Particle Number From Baseline to Week 24 | Change in LDL particle number | Baseline to 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atazanavir, Endothelial function, Treatment Experienced