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
調査の概要
詳細な説明
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.
研究の種類
入学 (予想される)
連絡先と場所
研究連絡先
- 名前:Patrick WG Mallon, MB BCh FRACP FRCPI PhD
- 電話番号:+353 716 6311
- メール:paddy.mallon@ucd.ie
研究場所
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London、イギリス、SW10 9NH
- 募集
- Chelsea & Westminster Hospital
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コンタクト:
- Anton Pozniak
- 電話番号:+44 20 8746 8000
- メール:anton.pozniak@chelwest.nhs.uk
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コンタクト:
- Graeme Moyle
- 電話番号:+44 20 8746 8000
- メール:gm@moyleg.demon.co.uk
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主任研究者:
- Anton Pozniak
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副調査官:
- Graeme Moyle
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
サンプリング方法
調査対象母集団
説明
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+
研究計画
研究はどのように設計されていますか?
デザインの詳細
この研究は何を測定していますか?
主要な結果の測定
結果測定 |
時間枠 |
---|---|
Change in ABCA1 mRNA expression in monocytes
時間枠:June 2013
|
June 2013
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協力者と研究者
捜査官
- 主任研究者: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
研究記録日
主要日程の研究
研究開始
一次修了 (予想される)
研究の完了 (予想される)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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