Clinical trial NCT00720590: Effect of the HIV Protease Inhibitors Atazanavir and Lopinavir/Ritonavir on Cardiovascular Disease Risk Factors
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Endothelial Dysfunction
Lead sponsor: Indiana University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2008-07-23
Enrollment: 30
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

Primary outcomes:
measure: Leg blood flow response to the intra-femoral artery infusion of methacholine chloride
timeFrame: Measured at Week 4
Secondary outcomes:
measure: Insulin sensitivity measured by the hyperinsulinemic euglycemic clamp study
timeFrame: Measured at Week 4
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
Study officials:
affiliation: Indiana University School of Medicine
name: Michael P. Dubé, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dube 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.