Effect of Raltegravir on Endothelial Function in HIV-Infected Patients
Status:
Completed
Trial end date:
2014-02-01
Target enrollment:
Participant gender:
Summary
Recent studies suggest that HIV patients are at increased risk for cardiovascular events;
however, the mechanisms underlying this increased risk remain unclear. Our group was one of
the first to demonstrate that HIV infection is independently associated with accelerated
atherosclerosis, as measured by carotid artery-intima media thickness (IMT), and that
HIV-associated inflammation may be driving this accelerated atherosclerosis. The mechanism by
which HIV disease independent of any drug-specific toxicity increases the risk of
cardiovascular disease during HAART is not known. We hypothesize that even well controlled
HIV infection is independently associated with cardiovascular risk and that further
decreasing HIV-associated inflammation adding newer antiretroviral agents will also decrease
cardiovascular risk.
We will perform a small clinical trial of approximately 50 HIV-infected patients each to
study the relationship between HIV infection, inflammation, thrombosis, atherogenic
lipoproteins, and measures of atherosclerosis. We propose the following specific aims: Aim 1:
To determine the influence of traditional and novel markers of inflammation on endothelial
function and IMT progression; Aim 2: To determine if "intensification" with raltegravir in
subjects on long-term antiretroviral therapy with clinically undetectable HIV RNA levels will
improve endothelial function, and to determine if this effect is mediated by alterations in
inflammatory markers, lipoproteins and/or thrombotic factors. For Aim 2, subjects from 2
randomized, double-blind, placebo-controlled raltegravir intensification studies will be
asked to co-enroll in this cardiovascular study.
Phase:
Phase 4
Details
Lead Sponsor:
University of California, San Francisco
Collaborators:
Merck Sharp & Dohme Corp. National Heart, Lung, and Blood Institute (NHLBI)