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HIV Reverse Cholesterol Transport Study (HIV RCTS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01670968
Recruitment Status : Unknown
Verified January 2013 by Patrick Mallon, University College Dublin.
Recruitment status was:  Recruiting
First Posted : August 23, 2012
Last Update Posted : January 28, 2013
Chelsea and Westminster NHS Foundation Trust
Information provided by (Responsible Party):
Patrick Mallon, University College Dublin

Brief Summary:

Primary Objective:

To examine changes in expression of genes [particularly ABCA1 and SREBP2] involved in reverse cholesterol transport (RCT) in monocytes from HIV-infected subjects starting antiretroviral therapy and the different effect of NNRTI and PI based regimens

Secondary Objective:

To examine changes in monocyte intracellular cholesterol content in HIV-infected subjects starting antiretroviral therapy and the different effect of NNRTI and PI based regimens

Condition or disease
HIV Dyslipidemia

Detailed Description:

HIV infection is associated with low HDL-cholesterol, an independent risk-factor for cardiovascular disease (CVD). NNRTI-based HAART increases HDL-c, with nevirapine shown to increase production of its major apolipoprotein ApoA-I. In contrast, initiation of PI-based HAART leads to persistently low HDL-c despite a reduction in HIV RNA and immunologic recovery.

HDL-c is formed through reverse cholesterol transport (RCT), the process where cholesterol is transferred from intracellular pools to circulating lipoproteins which are then eliminated by the liver. Accumulation of intracellular cholesterol in cells such as macrophages and their precursor (circulating monocytes) has been implicated in atherogenesis.

In vitro data suggests the HIV protein Nef directly interferes with cellular proteins involved in RCT such as ATP-binding cassette transporter A1 (ABCA1) in monocyte-derived macrophages. ABCA1 expression is controlled by peroxisome proliferator-activated receptor gamma (PPARG) and the intracellular cholesterol sensor sterol regulatory element binding protein 2 (SREBP2). In adipose tissue it is known that PI treatment downregulates SREBP and PPARG expression.

Preliminary work in the investigators lab has reproduced these findings in monocytes in untreated HIV infection in vivo and demonstrated relationships between gene expression for ABCA1, SREBP2, monocyte intracellular cholesterol and circulating lipoproteins. These early data suggest that defects in RCT determine intracellular cholesterol levels in HIV-infected subjects whereas increased LDL-c is a greater determinant of intracellular cholesterol in HIV negative subjects. This suggests a potentially pivotal role for RCT abnormalities in low HDL-c, increased intracellular cholesterol and atherogenesis in HIV infection.

The investigator's aim to examine the impact of initiation of ART with either PI or NNRTI on RCT in circulating monocytes in vivo and how this impact correlates with changes in amount and size of circulating HDL-c.

Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Effect of Antiretroviral Therapy and HIV on Reverse Cholesterol Transport in Blood( HIV Reverse Cholesterol Transport Study- HIV RCTS)
Study Start Date : September 2009
Estimated Primary Completion Date : June 2013
Estimated Study Completion Date : June 2013

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Primary Outcome Measures :
  1. Change in ABCA1 mRNA expression in monocytes [ Time Frame: June 2013 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Individuals starting antiretroviral therapy at the Mater Misericordiae University Hospital, Dublin, and Chelsea and Westminister Hospital, London

Inclusion Criteria:

  • > 18 years old
  • HIV-infected
  • Not currently on antiretroviral therapy (>6/12), but about to start

Exclusion Criteria:

  • On lipid lowering medication (statin / fibrate / niacin)
  • HCV Ab+

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01670968

Contact: Patrick WG Mallon, MB BCh FRACP FRCPI PhD +353 716 6311

United Kingdom
Chelsea & Westminster Hospital Recruiting
London, United Kingdom, SW10 9NH
Contact: Anton Pozniak    +44 20 8746 8000   
Contact: Graeme Moyle    +44 20 8746 8000   
Principal Investigator: Anton Pozniak         
Sub-Investigator: Graeme Moyle         
Sponsors and Collaborators
University College Dublin
Chelsea and Westminster NHS Foundation Trust
Principal Investigator: Patrick WG Mallon, FRACP FRCPI PhD HIV Molecular Research Group, UCD School of Medicine and Medical Sciences. Department of Infectious Diseases, Mater Misericordiae University Hospital and Mater Private Hospital

Responsible Party: Patrick Mallon, Associate Dean for Research and Innovation UCD School of Medicine and Medical Sciences, Consultant Infectious Diseases Physician, University College Dublin Identifier: NCT01670968     History of Changes
Other Study ID Numbers: HIV RCTS
First Posted: August 23, 2012    Key Record Dates
Last Update Posted: January 28, 2013
Last Verified: January 2013

Additional relevant MeSH terms:
Lipid Metabolism Disorders
Metabolic Diseases