HIV Reverse Cholesterol Transport Study (HIV RCTS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by University College Dublin
Sponsor:
Collaborator:
Chelsea and Westminster NHS Foundation Trust
Information provided by (Responsible Party):
Patrick Mallon, University College Dublin
ClinicalTrials.gov Identifier:
NCT01670968
First received: August 18, 2012
Last updated: January 25, 2013
Last verified: January 2013
  Purpose

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
HIV
Dyslipidemia

Study Type: Observational
Study Design: 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)

Resource links provided by NLM:


Further study details as provided by University College Dublin:

Primary Outcome Measures:
  • Change in ABCA1 mRNA expression in monocytes [ Time Frame: June 2013 ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: September 2009
Estimated Study Completion Date: June 2013
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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

Criteria

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+
  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: NCT01670968

Contacts
Contact: Patrick WG Mallon, MB BCh FRACP FRCPI PhD +353 716 6311 paddy.mallon@ucd.ie

Locations
United Kingdom
Chelsea & Westminster Hospital Recruiting
London, United Kingdom, SW10 9NH
Contact: Anton Pozniak    +44 20 8746 8000    anton.pozniak@chelwest.nhs.uk   
Contact: Graeme Moyle    +44 20 8746 8000    gm@moyleg.demon.co.uk   
Principal Investigator: Anton Pozniak         
Sub-Investigator: Graeme Moyle         
Sponsors and Collaborators
University College Dublin
Chelsea and Westminster NHS Foundation Trust
Investigators
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
  More Information

No publications provided

Responsible Party: Patrick Mallon, Associate Dean for Research and Innovation UCD School of Medicine and Medical Sciences, Consultant Infectious Diseases Physician, University College Dublin
ClinicalTrials.gov Identifier: NCT01670968     History of Changes
Other Study ID Numbers: HIV RCTS
Study First Received: August 18, 2012
Last Updated: January 25, 2013
Health Authority: Ireland: Research Ethics Committee

Additional relevant MeSH terms:
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on September 14, 2014