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

August 18, 2012
January 25, 2013
September 2009
June 2013   (final data collection date for primary outcome measure)
Change in ABCA1 mRNA expression in monocytes [ Time Frame: June 2013 ] [ Designated as safety issue: No ]
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Complete list of historical versions of study NCT01670968 on ClinicalTrials.gov Archive Site
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HIV Reverse Cholesterol Transport Study
The Effect of Antiretroviral Therapy and HIV on Reverse Cholesterol Transport in Blood( HIV Reverse Cholesterol Transport Study- HIV RCTS)

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

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.

Observational
Observational Model: Cohort
Time Perspective: Prospective
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Probability Sample

Individuals starting antiretroviral therapy at the Mater Misericordiae University Hospital, Dublin, and Chelsea and Westminister Hospital, London

  • HIV
  • Dyslipidemia
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
100
June 2013
June 2013   (final data collection date for primary outcome measure)

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+
Both
18 Years and older
No
Contact: Patrick WG Mallon, MB BCh FRACP FRCPI PhD +353 716 6311 paddy.mallon@ucd.ie
United Kingdom
 
NCT01670968
HIV RCTS
No
Patrick Mallon, University College Dublin
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
University College Dublin
January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP