Effect of Raltegravir on Endothelial Function in HIV-Infected Patients

Phase 4

Completed

Conditions: Cardiovascular Disease
HIV Infections
HIV Infection
Inflammation

Interventions: Drug: Placebo
Drug: raltegravir

Registration Number: NCT00843713

Lead Sponsor: University of California, San Francisco

Brief 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 56

Inclusion Criteria

Stable antiretroviral therapy for at least 12 months
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.
Screening plasma HIV RNA levels < 50 copies RNA/mL
>90% adherence to therapy within the preceding 30 days, as determined by self-report
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.
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

Ongoing or prior use of any integrase inhibitor or R5 inhibitor.
Patients who plan to modify existing antiretroviral therapy in the next 24 weeks for any reason
Serious illness requiring hospitalization or parental antibiotics within preceding 3 months
Concurrent or recent exposure to any immunomodulatory drugs
Advanced liver disease or active hepatitis B or C
Patients with systolic blood pressure <100/70
Starting or stopping statin therapy during the trial

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	For subjects assigned to the placebo group, patients will take a matching placebo pill of 400 mg by mouth twice daily for 24 weeks in addition to taking their current HIV medication
Raltegravir	raltegravir	For subjects assigned to the active comparator group, they will receive raltegravir at 400 mg by mouth twice daily for 24 weeks in addition to continuing to take their current HIV medication

Primary Outcome Measures

Name	Time	Method
Endothelial Function Measured by Brachial Artery Flow-mediated Dilation(FMD)	24 weeks	Measurements in the change of brachial artery diameter from pre and post treatment.

Secondary Outcome Measures