Effect of Raltegravir on Endothelial Function in HIV-Infected Patients
| Status: | Completed |
|---|---|
| Conditions: | Peripheral Vascular Disease, Cardiology, Infectious Disease, HIV / AIDS |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 12/14/2018 |
| Start Date: | January 2009 |
| End Date: | February 2014 |
A Randomized, Controlled Trial Assessing the Effects of Raltegravir Intensification on Endothelial Function in Treated HIV Infection
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.
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.
Inclusion Criteria:
1. Stable antiretroviral therapy for at least 12 months
2. All plasma HIV RNA levels within the past year must be below level of detection (< 50
copies RNA/mL), although isolated single values > 50 but < 200 copies will be allowed.
3. Screening plasma HIV RNA levels < 50 copies RNA/mL
4. >90% adherence to therapy within the preceding 30 days, as determined by self-report
5. Females of childbearing potential must have a negative serum pregnancy test at
screening and agree to use a double-barrier method of contraception throughout the
study period.
6. CD4<350 cells/mm3 for at least one year ("immunologic non-responder") or CD4>=350
cells/mm3 for at least one year ("immunologic responder").
Exclusion Criteria:
1. Ongoing or prior use of any integrase inhibitor or R5 inhibitor.
2. Patients who plan to modify existing antiretroviral therapy in the next 24 weeks for
any reason
3. Serious illness requiring hospitalization or parental antibiotics within preceding 3
months
4. Concurrent or recent exposure to any immunomodulatory drugs
5. Advanced liver disease or active hepatitis B or C
6. Patients with systolic blood pressure <100/70
7. Starting or stopping statin therapy during the trial
We found this trial at
1
site
Click here to add this to my saved trials
