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

Endothelial Dysfunction Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00720590
• Other study ID #: 573
• Secondary ID: R01HL072711R01HL
• Status: Completed
• Phase: N/A
• First received: July 21, 2008
• Last updated: October 23, 2017
• Start date: November 2003
• Est. completion date: October 2006

Study information

• Verified date: July 2008
• Source: Indiana University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: October 2006
• Est. primary completion date: September 2006
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Healthy and lean with normal lipids

• Not infected with HIV or viral hepatitis

Exclusion Criteria:

Related Conditions & MeSH terms

• Endothelial Dysfunction

Intervention

Drug:
• Atazanavir
400 mg of atazanavir (two 200-mg capsules) per day for 4 weeks
• 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
• Placebo
Daily dose of placebo for 4 weeks

Locations

Country	Name	City	State
United States	Indiana University School of Medicine	Indianapolis	Indiana

Sponsors (2)

Lead Sponsor	Collaborator
Indiana University	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Leg blood flow response to the intra-femoral artery infusion of methacholine chloride		Measured at Week 4
Secondary	Insulin sensitivity measured by the hyperinsulinemic euglycemic clamp study		Measured at Week 4