HIV Infection, Hyperlipidemia
Conditions
Keywords
Atazanavir, Endothelial function, Treatment Experienced
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.
Interventions
DRUGAtazanavir
atazanavir 400 mg once daily
DRUGcurrent antiretroviral regimen
Continue current antiretroviral regimen for 24 weeks, single or RTV-boosted PI plus \> 2 NRTIs
Sponsors
Bristol-Myers Squibb
Northwestern University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Argentina, Italy, United States
Participant flow
Recruitment details
Recruitment period June 2005 to November 2007 at four clinics in the United States, one in Italy, and one in Argentina
Participants by arm
| Arm | Count |
|---|---|
| Atazanavir Switch 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. | 26 |
| Control (Continue Protease Inhibitor) ARM B: Continue current antiretroviral regimen (single or RTV-boosted PI plus \> 2 NRTIs) for 24 weeks | 24 |
| Total | 50 |
Baseline characteristics
| Characteristic | Atazanavir Switch | Control (Continue Protease Inhibitor) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants | 24 Participants | 50 Participants |
| Age Continuous | 43 years | 43 years | 43 years |
| Region of Enrollment Argentina | 8 participants | 7 participants | 15 participants |
| Region of Enrollment Italy | 1 participants | 2 participants | 3 participants |
| Region of Enrollment United States | 17 participants | 15 participants | 32 participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 8 Participants |
| Sex: Female, Male Male | 22 Participants | 20 Participants | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 26 | 0 / 24 |
| serious Total, serious adverse events | 0 / 26 | 0 / 24 |
Outcome results
Primary
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
Time frame: Baseline to week 24
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atazanavir Switch | Percentage Change in Brachial Artery Flow Mediated (FMD) Vasodilation Between Arms From Baseline to Week 24 | -1.14 percentage change |
| Control (Continue Protease Inhibitor) | Percentage Change in Brachial Artery Flow Mediated (FMD) Vasodilation Between Arms From Baseline to Week 24 | 0.25 percentage change |
p-value: 0.60195% CI: [-2.08, 1.312]Wilcoxon (Mann-Whitney)
Secondary
Change in Total Cholesterol Levels From Baseline to Week 24
Total cholesterol level changes within and between arms
Time frame: Baseline to 24 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atazanavir Switch | Change in Total Cholesterol Levels From Baseline to Week 24 | -25 mg/dL |
| Control (Continue Protease Inhibitor) | Change in Total Cholesterol Levels From Baseline to Week 24 | 2 mg/dL |
p-value: <0.009Wilcoxon (Mann-Whitney)
Secondary
Changes in LDL Particle Number From Baseline to Week 24
Change in LDL particle number
Time frame: Baseline to 24 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atazanavir Switch | Changes in LDL Particle Number From Baseline to Week 24 | -194 nmol/l |
| Control (Continue Protease Inhibitor) | Changes in LDL Particle Number From Baseline to Week 24 | -116 nmol/l |
p-value: 0.141Wilcoxon (Mann-Whitney)