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