Effect of the HIV Protease Inhibitors Atazanavir and Lopinavir/Ritonavir on Cardiovascular Disease Risk Factors
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ClinicalTrials.gov Identifier: NCT00720590 |
Recruitment Status
:
Completed
First Posted
: July 23, 2008
Last Update Posted
: October 25, 2017
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Endothelial Dysfunction | Drug: Atazanavir Drug: Lopinavir/ritonavir Drug: Placebo | Not Applicable |
Antiretroviral therapy for HIV, particularly with the use of PIs, is associated with an increased risk of heart attack. Specific cardiovascular side effects seen with the use of some PIs include insulin resistance, abnormal blood lipid levels, and endothelial dysfunction (abnormalities in the cells that line the inner surface of blood vessels). Past studies have shown that treatment with indinavir, an older PI, results in significant endothelial dysfunction, which may be the main cause for the increase in cardiovascular risk. Indinavir is now seldom used in clinical practice, and the newer PIs atazanavir and combination lopinavir/ritonavir now account for nearly 70% of total PI use in the United States. It is not known what effect these new PIs have on endothelial dysfunction. This study will compare the effects of atazanavir, lopinavir/ritonavir, and placebo on certain cardiovascular disease risk factors, including abnormal glucose metabolism and endothelial dysfunction, in healthy people without HIV.
Participation in this study will last 4 weeks. All participants will undergo initial assessments that will include various vascular and metabolic evaluations. Body weight, height, basal heart rate, and systolic and diastolic blood pressure will also be measured. Participants will then be assigned randomly to receive 4 weeks of treatment with 400 mg of atazanavir per day plus placebo, 400 mg/100 mg of lopinavir/ritonavir twice per day plus placebo, or placebos for both drugs per day. Upon completing the 4 weeks of treatment, participants will repeat the initial assessments.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 30 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Triple (Participant, Care Provider, Investigator) |
Primary Purpose: | Other |
Official Title: | Effect of HIV-1 Protease Inhibitors on Endothelial Function and Glucose Metabolism in Normal, HIV-Uninfected Subjects: Atazanavir or Lopinavir/Ritonavir or Placebo |
Study Start Date : | November 2003 |
Actual Primary Completion Date : | September 2006 |
Actual Study Completion Date : | October 2006 |

Arm | Intervention/treatment |
---|---|
Experimental: 1
Participants will receive treatment with atazanavir and placebo lopinavir/ritonavir.
|
Drug: Atazanavir
400 mg of atazanavir (two 200-mg capsules) per day for 4 weeks
Drug: Placebo
Daily dose of placebo for 4 weeks
|
Experimental: 2
Participants will receive treatment with lopinavir/ritonavir and placebo atazanavir.
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Drug: Lopinavir/ritonavir
400 mg/100 mg of lopinavir/ritonavir (three soft-gel capsules, each containing 133.3 mg lopinavir and 33.3 mg ritonavir) twice per day with food for 4 weeks
Drug: Placebo
Daily dose of placebo for 4 weeks
|
Placebo Comparator: 3
Participants will receive treatment with placebos for both drugs.
|
Drug: Placebo
Daily dose of placebo for 4 weeks
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- Leg blood flow response to the intra-femoral artery infusion of methacholine chloride [ Time Frame: Measured at Week 4 ]
- Insulin sensitivity measured by the hyperinsulinemic euglycemic clamp study [ Time Frame: Measured at Week 4 ]

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Ages Eligible for Study: | 18 Years to 65 Years (Adult) |
Sexes Eligible for Study: | Male |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
- Healthy and lean with normal lipids
- Not infected with HIV or viral hepatitis
Exclusion Criteria:

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00720590
United States, Indiana | |
Indiana University School of Medicine | |
Indianapolis, Indiana, United States, 46202 |
Principal Investigator: | Michael P. Dubé, MD | Indiana University School of Medicine |
Publications of Results:
Responsible Party: | Michael P. Dubé, MD, Indiana University School of Medicine |
ClinicalTrials.gov Identifier: | NCT00720590 History of Changes |
Other Study ID Numbers: |
573 R01HL072711 ( U.S. NIH Grant/Contract ) R01HL072711-01 ( U.S. NIH Grant/Contract ) |
First Posted: | July 23, 2008 Key Record Dates |
Last Update Posted: | October 25, 2017 |
Last Verified: | July 2008 |
Additional relevant MeSH terms:
Ritonavir Lopinavir Atazanavir Sulfate HIV Protease Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |
Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors |