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

Indiana University

Status: Completed

Conditions: Endothelial Dysfunction

Treatments: Drug: Atazanavir; Drug: Placebo; Drug: Lopinavir/ritonavir

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00720590

R01HL072711-01 (U.S. NIH Grant/Contract)

573

R01HL072711 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 patients

Sex: Male

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

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

Exclusion Criteria:

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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30 participants in 3 patient groups, including a placebo group

1

Experimental group

Description:

Participants will receive treatment with atazanavir and placebo lopinavir/ritonavir.

Treatment:

Drug: Placebo

Drug: Atazanavir

2

Experimental group

Description:

Participants will receive treatment with lopinavir/ritonavir and placebo atazanavir.

Treatment:

Drug: Placebo

Drug: Lopinavir/ritonavir

3

Placebo Comparator group

Description:

Participants will receive treatment with placebos for both drugs.

Treatment:

Drug: Placebo