Effect of the HIV Protease Inhibitors Atazanavir and Lopinavir/Ritonavir on Cardiovascular Disease Risk Factors

Not Applicable

Completed

• Conditions: Endothelial Dysfunction
• Interventions: Drug: Atazanavir; Drug: Lopinavir/ritonavir; Drug: Placebo

• Registration Number: NCT00720590
• Lead Sponsor: Indiana University

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.

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 Timeline

• Study Start: 2003-11
• Primary Completion: 2006-09
• Study Completion: 2006-10
• Status Verified: 2008-07
• Study First Submitted: 2008-07-21
• Study First Submitted QC: 2008-07-21
• Study First Posted: 2008-07-23
• Last Update Submitted: 2017-10-23
• Last Update Posted: 2017-10-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 30

Inclusion Criteria

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Atazanavir	Participants will receive treatment with atazanavir and placebo lopinavir/ritonavir.
1	Placebo	Participants will receive treatment with atazanavir and placebo lopinavir/ritonavir.
2	Lopinavir/ritonavir	Participants will receive treatment with lopinavir/ritonavir and placebo atazanavir.
2	Placebo	Participants will receive treatment with lopinavir/ritonavir and placebo atazanavir.
3	Placebo	Participants will receive treatment with placebos for both drugs.

Primary Outcome Measures

Name	Time	Method
Leg blood flow response to the intra-femoral artery infusion of methacholine chloride	Measured at Week 4

Secondary Outcome Measures

Name	Time	Method
Insulin sensitivity measured by the hyperinsulinemic euglycemic clamp study	Measured at Week 4

Trial Locations

Locations (1)

Indiana University School of Medicine; 🇺🇸 Indianapolis, Indiana, United States