HIV Reverse Cholesterol Transport Study (HIV RCTS)

March 24, 2020 updated by: Patrick Mallon, University College Dublin

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

Study Overview

Status

Unknown

Conditions

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

Enrollment (Anticipated)

100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Patrick WG Mallon, MB BCh FRACP FRCPI PhD
  • Phone Number: +353 716 6311
  • Email: paddy.mallon@ucd.ie

Study Locations

      • London, United Kingdom, SW10 9NH
        • Recruiting
        • Chelsea & Westminster Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Anton Pozniak
        • Sub-Investigator:
          • Graeme Moyle

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

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

Description

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+

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change in ABCA1 mRNA expression in monocytes
Time Frame: June 2013
June 2013

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2009

Primary Completion (Anticipated)

May 1, 2020

Study Completion (Anticipated)

June 1, 2020

Study Registration Dates

First Submitted

August 18, 2012

First Submitted That Met QC Criteria

August 22, 2012

First Posted (Estimate)

August 23, 2012

Study Record Updates

Last Update Posted (Actual)

March 25, 2020

Last Update Submitted That Met QC Criteria

March 24, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

Other Study ID Numbers

  • HIV RCTS

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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