Endothelial Dysfunction as a Risk Factor in HIV Study
Status:
Completed
Trial end date:
2005-10-01
Target enrollment:
Participant gender:
Summary
Highly active antiretroviral therapy (HAART) has proven effective in altering the natural
history of HIV infection in many patients. However, this therapy may not be sustainable
because of the toxicities of the medications. Evidence suggests that HIV-infected patients on
HAART may be at risk for premature coronary artery disease. The exact cause is unknown. It is
possible that the medications directly affect the endothelium (the lining of the arteries
that supply blood to the heart) and lead to premature heart disease. Or because the
medications cause lipid abnormalities (high cholesterol) and a condition of relative insulin
resistance, in which the body has a difficult time processing sugars; known risk factors for
endothelial dysfunction and heart disease. Therapeutic intervention that reverses these lipid
abnormalities and/or insulin resistance may lower these risk factors, normalize endothelial
function, and decrease the risk of heart disease.
This protocol aims to assess endothelial function among a group of HIV-infected patients with
varying degrees of viral activity and levels of immune function on a variety of HAART
regimens. It also aims to evaluate the effect of three different medications on lipids,
insulin resistance, and thus endothelial function. Understanding the factors involved in
causing endothelial dysfunction will help better characterize the relative risks and benefits
of early versus late and continuous versus intermittent HAART therapy. The research may offer
some insights into the causes of premature heart disease among HIV-infected patients on HAART
that could be more thoroughly investigated in subsequent clinical trials.
A total of 75 patients will be recruited: 25 for each arm of the study. Each arm evaluates
the potential benefit of a particular medication and will enroll sequentially. An endothelial
function test will be performed on an outpatient basis. The first 25 patients will be
assigned at random to receive pravastatin sodium or placebo; the next 25 will receive
gemfibrozil or placebo; the final 25 will receive rosiglitazone or placebo. Patients will
take the pills for 6 weeks, no pills for the next 4 weeks, and then the opposite treatment
for 6 more weeks. Two weeks after the start of the study drug, blood will be taken to check
for potential toxic side effects. After each 6-week treatment, blood will be drawn and
endothelial function tests will be performed.
Phase:
Phase 1
Details
Lead Sponsor:
National Institutes of Health Clinical Center (CC)