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

Sponsor:

Collaborator:

National Heart, Lung, and Blood Institute (NHLBI)

Information provided by:

Indiana University

Study Description

Brief Summary:

HIV protease inhibitors (PIs) are a class of antiretroviral drugs used to inhibit viral replication. They do so by interfering with a key step in the replication process. Some HIV PIs have been associated with an increased risk of adverse cardiovascular side effects. Further study is needed, however, to assess the full extent of effect of newer HIV PIs, including atazanavir and lopinavir/ritonavir, on cardiovascular disease risk. This study will compare the effects of atazanavir, lopinavir/ritonavir, and placebo on certain cardiovascular disease risk factors in healthy people without HIV.

Condition or disease	Intervention/treatment	Phase
Endothelial Dysfunction	Drug: Atazanavir Drug: Lopinavir/ritonavir Drug: Placebo	Not Applicable

Detailed Description:

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 Design


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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Ritonavir Lopinavir Atazanavir Atazanavir sulfate

U.S. FDA Resources

Arms and Interventions

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.	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

Outcome Measures

Primary Outcome Measures :

Leg blood flow response to the intra-femoral artery infusion of methacholine chloride [ Time Frame: Measured at Week 4 ]

Secondary Outcome Measures :

Insulin sensitivity measured by the hyperinsulinemic euglycemic clamp study [ Time Frame: Measured at Week 4 ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years to 65 Years (Adult)
Sexes Eligible for Study:	Male
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Healthy and lean with normal lipids
Not infected with HIV or viral hepatitis

Exclusion Criteria:

Contacts and Locations

Information from the National Library of Medicine

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

Locations


United States, Indiana
Indiana University School of Medicine
Indianapolis, Indiana, United States, 46202

Sponsors and Collaborators

Indiana University

National Heart, Lung, and Blood Institute (NHLBI)

Investigators


Principal Investigator:	Michael P. Dubé, MD	Indiana University School of Medicine

More Information

Publications of Results:

Dubé MP, Shen C, Greenwald M, Mather KJ. No impairment of endothelial function or insulin sensitivity with 4 weeks of the HIV protease inhibitors atazanavir or lopinavir-ritonavir in healthy subjects without HIV infection: a placebo-controlled trial. Clin Infect Dis. 2008 Aug 15;47(4):567-74. doi: 10.1086/590154.


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

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