Switch to Atazanavir and Brachial Artery Reactivity (SABAR) Study

• Change in Total Cholesterol Levels From Baseline to Week 24 [ Time Frame: Baseline to 24 weeks ] [ Designated as safety issue: No ]
  Total cholesterol level changes within and between arms
• Changes in LDL Particle Number From Baseline to Week 24 [ Time Frame: Baseline to 24 weeks ] [ Designated as safety issue: No ]
  Change in LDL particle number

• To compare the changes in LDL particle number, diameter, insulin sensitivity from baseline to week 24 between arms.
• To evaluate change in FMD from baseline to week 24 within each arm.
• To evaluate lipid levels and to relate their changes to FMD and changes in FMD both within and between arms

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

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.

• HIV Infection
• Hyperlipidemia

• Drug: Atazanavir
  atazanavir 400 mg once daily
  Other Name: Reyataz
• Drug: current antiretroviral regimen
  Continue current antiretroviral regimen for 24 weeks, single or RTV-boosted PI plus > 2 NRTIs

• Experimental: A

  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.

  Intervention: Drug: Atazanavir
• Active Comparator: B
  ARM B: Continue current antiretroviral regimen (single or RTV-boosted PI plus > 2 NRTIs) for 24 weeks
  Intervention: Drug: current antiretroviral regimen

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