Effect of Raltegravir on Endothelial Function in HIV-Infected Patients - Full Text View

Purpose

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.

Condition	Intervention	Phase
HIV Infection Inflammation Cardiovascular Disease HIV Infections	Drug: raltegravir Drug: Placebo	Phase 4


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Randomized, Controlled Trial Assessing the Effects of Raltegravir Intensification on Endothelial Function in Treated HIV Infection

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Raltegravir Raltegravir potassium

U.S. FDA Resources

Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:

Endothelial Function Measured by Brachial Artery Flow-mediated Dilation(FMD) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Measurements in the change of brachial artery diameter from pre and post treatment.


Enrollment:	56
Study Start Date:	January 2009
Study Completion Date:	February 2014
Primary Completion Date:	November 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: 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	Drug: Placebo For the patient assigned to the placebo group, subjects will take a matching placebo pill 400mg to be taken by mouth twice daily for 24 weeks in addition to taking their current HIV medication
Active Comparator: 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	Drug: raltegravir For patients assigned to the raltegravir group, subjects will receive raltegravir 400mg to be taken by mouth twice daily for 24 weeks in addition to taking their current HIV medication

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00843713

Locations


United States, California
University of California, San Francisco
San Francisco, California, United States, 94110

Sponsors and Collaborators

University of California, San Francisco

National Heart, Lung, and Blood Institute (NHLBI)

Merck Sharp & Dohme Corp.

Investigators


Principal Investigator:	Priscilla Hsue, MD	San Francisco General Hospital

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Hatano H, Scherzer R, Wu Y, Harvill K, Maka K, Hoh R, Sinclair E, Palmer S, Martin JN, Busch MP, Deeks SG, Hsue PY. A randomized controlled trial assessing the effects of raltegravir intensification on endothelial function in treated HIV infection. J Acquir Immune Defic Syndr. 2012 Nov 1;61(3):317-25. doi: 10.1097/QAI.0b013e31826e7d0f.


Responsible Party:	Priscilla Hsue, Associate Professor, University of California, San Francisco
ClinicalTrials.gov Identifier:	NCT00843713 History of Changes
Other Study ID Numbers:	1R01HL095130-01
Study First Received:	February 12, 2009
Results First Received:	January 30, 2015
Last Updated:	May 26, 2015
Health Authority:	United States: Institutional Review Board

Keywords provided by University of California, San Francisco:


HIV endothelium inflammation Treatment Experienced

Additional relevant MeSH terms:


HIV Infections Acquired Immunodeficiency Syndrome Infection Communicable Diseases Inflammation Cardiovascular Diseases Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes	Immune System Diseases Slow Virus Diseases Pathologic Processes Raltegravir Potassium Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents HIV Integrase Inhibitors Integrase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 23, 2016