Switch to Atazanavir and Brachial Artery Reactivity (SABAR) Study

Phase 3

Completed

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
B	current antiretroviral regimen	ARM B: Continue current antiretroviral regimen (single or RTV-boosted PI plus \> 2 NRTIs) for 24 weeks
A	Atazanavir	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.

Primary Outcome Measures

Name	Time	Method
Percentage Change in Brachial Artery Flow Mediated (FMD) Vasodilation Between Arms From Baseline to Week 24	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

Secondary Outcome Measures

Name	Time	Method
Change in Total Cholesterol Levels From Baseline to Week 24	Baseline to 24 weeks	Total cholesterol level changes within and between arms
Changes in LDL Particle Number From Baseline to Week 24	Baseline to 24 weeks	Change in LDL particle number

Locations (7): Universita degli studi di Modena e Reggio Emilia
🇮🇹
Modena, Italy
ACLIRES - Argentina S.R.L.
🇦🇷
Buenos Aires, Argentina
University of California
🇺🇸
San Diego, California, United States
Northwestern Universtiy
🇺🇸
Chicago, Illinois, United States
University of Cincinnati
🇺🇸
Cincinnati, Ohio, United States
Indiana University
🇺🇸
Indianapolis, Indiana, United States
University of Wisconsin
🇺🇸
Madison, Wisconsin, United States