HIV Reverse Cholesterol Transport Study (HIV RCTS)
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
研究概览
详细说明
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.
研究类型
注册 (预期的)
联系人和位置
学习地点
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London、英国、SW10 9NH
- 招聘中
- Chelsea & Westminster Hospital
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接触：
- Anton Pozniak
- 电话号码：+44 20 8746 8000
- 邮箱：anton.pozniak@chelwest.nhs.uk
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接触：
- Graeme Moyle
- 电话号码：+44 20 8746 8000
- 邮箱：gm@moyleg.demon.co.uk
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首席研究员：
- Anton Pozniak
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副研究员：
- Graeme Moyle
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
取样方法
研究人群
描述
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+
学习计划
研究是如何设计的？
设计细节
研究衡量的是什么？
主要结果指标
结果测量 |
大体时间 |
|---|---|
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Change in ABCA1 mRNA expression in monocytes
大体时间：June 2013
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June 2013
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合作者和调查者
调查人员
- 首席研究员：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
研究记录日期
研究主要日期
学习开始
初级完成 (预期的)
研究完成 (预期的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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