Plasma Lipidomic Profiling of Treated HIV-Positive Individuals and the Implications for Cardiovascular Risk Prediction
Identifieur interne : 001407 ( Pmc/Checkpoint ); précédent : 001406; suivant : 001408Plasma Lipidomic Profiling of Treated HIV-Positive Individuals and the Implications for Cardiovascular Risk Prediction
Auteurs : Gerard Wong [Australie] ; Janine M. Trevillyan [Australie] ; Benoit Fatou [Australie] ; Michelle Cinel [Australie] ; Jacquelyn M. Weir [Australie] ; Jennifer F. Hoy [Australie] ; Peter J. Meikle [Australie]Source :
- PLoS ONE [ 1932-6203 ] ; 2014.
Abstract
The increased risk of coronary artery disease in human immunodeficiency virus (HIV) positive patients is collectively contributed to by the human immunodeficiency virus and antiretroviral-associated dyslipidaemia. In this study, we investigate the characterisation of the plasma lipid profiles of treated HIV patients and the relationship of 316 plasma lipid species across multiple lipid classes with the risk of future cardiovascular events in HIV- positive patients.
In a retrospective case-control study, we analysed plasma lipid profiles of 113 subjects. Cases (n = 23) were HIV-positive individuals with a stored blood sample available 12 months prior to their diagnosis of coronary artery disease (CAD). They were age and sex matched to HIV-positive individuals without a diagnosis of CAD (n = 45) and with healthy HIV-negative volunteers (n = 45).
Association of plasma lipid species and classes with HIV infection and cardiovascular risk in HIV were determined. In multiple logistic regression, we identified 83 lipids species and 7 lipid classes significantly associated with HIV infection and a further identified 74 lipid species and 8 lipid classes significantly associated with future cardiovascular events in HIV-positive subjects. Risk prediction models incorporating lipid species attained an area under the receiver operator characteristic curve (AUC) of 0.78 (0.775, 0.785)) and outperformed all other tested markers and risk scores in the identification of HIV-positive subjects with increased risk of cardiovascular events.
Our results demonstrate that HIV-positive patients have significant differences in their plasma lipid profiles compared with healthy HIV-negative controls and that numerous lipid species were significantly associated with elevated cardiovascular risk. This suggests a potential novel application for plasma lipids in cardiovascular risk screening of HIV-positive patients.
Url:
DOI: 10.1371/journal.pone.0094810
PubMed: 24733512
PubMed Central: 3986244
Affiliations:
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Trevillyan</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Infectious Diseases Unit, Alfred Hospital, Melbourne, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Infectious Diseases Unit, Alfred Hospital, Melbourne, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Department of Infectious Diseases, Faculty of Medicine, Nursing and Health Science, Monash University, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Infectious Diseases, Faculty of Medicine, Nursing and Health Science, Monash University, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Fatou, Benoit" sort="Fatou, Benoit" uniqKey="Fatou B" first="Benoit" last="Fatou">Benoit Fatou</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Baker IDI Heart and Diabetes Institute, Melbourne, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation><affiliation><nlm:aff id="aff4"><addr-line>University of Sciences and Technologies of Lille, Lille France</addr-line></nlm:aff><wicri:noCountry code="subfield">Lille France</wicri:noCountry></affiliation></author><author><name sortKey="Cinel, Michelle" sort="Cinel, Michelle" uniqKey="Cinel M" first="Michelle" last="Cinel">Michelle Cinel</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Baker IDI Heart and Diabetes Institute, Melbourne, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Weir, Jacquelyn M" sort="Weir, Jacquelyn M" uniqKey="Weir J" first="Jacquelyn M." last="Weir">Jacquelyn M. 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Hoy</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Infectious Diseases Unit, Alfred Hospital, Melbourne, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Infectious Diseases Unit, Alfred Hospital, Melbourne, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Department of Infectious Diseases, Faculty of Medicine, Nursing and Health Science, Monash University, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Infectious Diseases, Faculty of Medicine, Nursing and Health Science, Monash University, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Meikle, Peter J" sort="Meikle, Peter J" uniqKey="Meikle P" first="Peter J." last="Meikle">Peter J. Meikle</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Baker IDI Heart and Diabetes Institute, Melbourne, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24733512</idno><idno type="pmc">3986244</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3986244</idno><idno type="RBID">PMC:3986244</idno><idno type="doi">10.1371/journal.pone.0094810</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">002B59</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002B59</idno><idno type="wicri:Area/Pmc/Curation">002A09</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">002A09</idno><idno type="wicri:Area/Pmc/Checkpoint">001407</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">001407</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Plasma Lipidomic Profiling of Treated HIV-Positive Individuals and the Implications for Cardiovascular Risk Prediction</title><author><name sortKey="Wong, Gerard" sort="Wong, Gerard" uniqKey="Wong G" first="Gerard" last="Wong">Gerard Wong</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Baker IDI Heart and Diabetes Institute, Melbourne, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Trevillyan, Janine M" sort="Trevillyan, Janine M" uniqKey="Trevillyan J" first="Janine M." last="Trevillyan">Janine M. Trevillyan</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Infectious Diseases Unit, Alfred Hospital, Melbourne, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Infectious Diseases Unit, Alfred Hospital, Melbourne, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Department of Infectious Diseases, Faculty of Medicine, Nursing and Health Science, Monash University, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Infectious Diseases, Faculty of Medicine, Nursing and Health Science, Monash University, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Fatou, Benoit" sort="Fatou, Benoit" uniqKey="Fatou B" first="Benoit" last="Fatou">Benoit Fatou</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Baker IDI Heart and Diabetes Institute, Melbourne, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation><affiliation><nlm:aff id="aff4"><addr-line>University of Sciences and Technologies of Lille, Lille France</addr-line></nlm:aff><wicri:noCountry code="subfield">Lille France</wicri:noCountry></affiliation></author><author><name sortKey="Cinel, Michelle" sort="Cinel, Michelle" uniqKey="Cinel M" first="Michelle" last="Cinel">Michelle Cinel</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Baker IDI Heart and Diabetes Institute, Melbourne, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Weir, Jacquelyn M" sort="Weir, Jacquelyn M" uniqKey="Weir J" first="Jacquelyn M." last="Weir">Jacquelyn M. Weir</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Baker IDI Heart and Diabetes Institute, Melbourne, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Hoy, Jennifer F" sort="Hoy, Jennifer F" uniqKey="Hoy J" first="Jennifer F." last="Hoy">Jennifer F. Hoy</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Infectious Diseases Unit, Alfred Hospital, Melbourne, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Infectious Diseases Unit, Alfred Hospital, Melbourne, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Department of Infectious Diseases, Faculty of Medicine, Nursing and Health Science, Monash University, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Infectious Diseases, Faculty of Medicine, Nursing and Health Science, Monash University, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Meikle, Peter J" sort="Meikle, Peter J" uniqKey="Meikle P" first="Peter J." last="Meikle">Peter J. Meikle</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Baker IDI Heart and Diabetes Institute, Melbourne, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>The increased risk of coronary artery disease in human immunodeficiency virus (HIV) positive patients is collectively contributed to by the human immunodeficiency virus and antiretroviral-associated dyslipidaemia. In this study, we investigate the characterisation of the plasma lipid profiles of treated HIV patients and the relationship of 316 plasma lipid species across multiple lipid classes with the risk of future cardiovascular events in HIV- positive patients.</p></sec><sec><title>Methods</title><p>In a retrospective case-control study, we analysed plasma lipid profiles of 113 subjects. Cases (n = 23) were HIV-positive individuals with a stored blood sample available 12 months prior to their diagnosis of coronary artery disease (CAD). They were age and sex matched to HIV-positive individuals without a diagnosis of CAD (n = 45) and with healthy HIV-negative volunteers (n = 45).</p></sec><sec><title>Results</title><p>Association of plasma lipid species and classes with HIV infection and cardiovascular risk in HIV were determined. In multiple logistic regression, we identified 83 lipids species and 7 lipid classes significantly associated with HIV infection and a further identified 74 lipid species and 8 lipid classes significantly associated with future cardiovascular events in HIV-positive subjects. Risk prediction models incorporating lipid species attained an area under the receiver operator characteristic curve (AUC) of 0.78 (0.775, 0.785)) and outperformed all other tested markers and risk scores in the identification of HIV-positive subjects with increased risk of cardiovascular events.</p></sec><sec><title>Conclusions</title><p>Our results demonstrate that HIV-positive patients have significant differences in their plasma lipid profiles compared with healthy HIV-negative controls and that numerous lipid species were significantly associated with elevated cardiovascular risk. 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Orband-Miller</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shahmanesh, M" uniqKey="Shahmanesh M">M Shahmanesh</name></author><author><name sortKey="Das, S" uniqKey="Das S">S Das</name></author><author><name sortKey="Stolinski, M" uniqKey="Stolinski M">M Stolinski</name></author><author><name sortKey="Shojaee Moradie, F" uniqKey="Shojaee Moradie F">F Shojaee-Moradie</name></author><author><name sortKey="Jackson, Nc" uniqKey="Jackson N">NC Jackson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Spector, Aa" uniqKey="Spector A">AA Spector</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Carpentier, A" uniqKey="Carpentier A">A Carpentier</name></author><author><name sortKey="Patterson, Bw" uniqKey="Patterson B">BW Patterson</name></author><author><name sortKey="Uffelman, Kd" uniqKey="Uffelman K">KD Uffelman</name></author><author><name sortKey="Salit, I" uniqKey="Salit I">I Salit</name></author><author><name sortKey="Lewis, Gf" uniqKey="Lewis G">GF Lewis</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS One</journal-id><journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plosone</journal-id><journal-title-group><journal-title>PLoS ONE</journal-title></journal-title-group><issn pub-type="epub">1932-6203</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">24733512</article-id><article-id pub-id-type="pmc">3986244</article-id><article-id pub-id-type="publisher-id">PONE-D-14-00741</article-id><article-id pub-id-type="doi">10.1371/journal.pone.0094810</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Biology and Life Sciences</subject><subj-group><subject>Biochemistry</subject><subj-group><subject>Biomarkers</subject><subject>Lipids</subject></subj-group></subj-group><subj-group><subject>Microbiology</subject><subj-group><subject>Medical Microbiology</subject><subj-group><subject>Microbial Pathogens</subject><subj-group><subject>Viral Pathogens</subject><subj-group><subject>Immunodeficiency Viruses</subject><subj-group><subject>HIV</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Medicine and health sciences</subject><subj-group><subject>Cardiology</subject></subj-group><subj-group><subject>Diagnostic Medicine</subject></subj-group><subj-group><subject>Epidemiology</subject><subj-group><subject>Cardiovascular disease epidemiology</subject><subject>Clinical epidemiology</subject><subject>HIV epidemiology</subject></subj-group></subj-group><subj-group><subject>Infectious Diseases</subject><subj-group><subject>Viral Diseases</subject></subj-group></subj-group><subj-group><subject>Pathology and Laboratory Medicine</subject></subj-group><subj-group><subject>Vascular Medicine</subject><subj-group><subject>Atherosclerosis</subject></subj-group></subj-group></subj-group></article-categories><title-group><article-title>Plasma Lipidomic Profiling of Treated HIV-Positive Individuals and the Implications for Cardiovascular Risk Prediction</article-title><alt-title alt-title-type="running-head">HIV Lipidomic Profiling and Cardiovascular Risk</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Wong</surname><given-names>Gerard</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Trevillyan</surname><given-names>Janine M.</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Fatou</surname><given-names>Benoit</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Cinel</surname><given-names>Michelle</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Weir</surname><given-names>Jacquelyn M.</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hoy</surname><given-names>Jennifer F.</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="aff" rid="aff3"><sup>3</sup></xref><xref ref-type="author-notes" rid="fn1"><sup>¤</sup></xref></contrib><contrib contrib-type="author"><name><surname>Meikle</surname><given-names>Peter J.</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib></contrib-group><aff id="aff1"><label>1</label><addr-line>Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia</addr-line></aff><aff id="aff2"><label>2</label><addr-line>Infectious Diseases Unit, Alfred Hospital, Melbourne, Victoria, Australia</addr-line></aff><aff id="aff3"><label>3</label><addr-line>Department of Infectious Diseases, Faculty of Medicine, Nursing and Health Science, Monash University, Victoria, Australia</addr-line></aff><aff id="aff4"><label>4</label><addr-line>University of Sciences and Technologies of Lille, Lille France</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Monleon</surname><given-names>Daniel</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1"><addr-line>Instituto de Investigación Sanitaria INCLIVA, Spain</addr-line></aff><author-notes><corresp id="cor1">* E-mail: <email>peter.meikle@bakeridi.edu.au</email></corresp><fn fn-type="conflict"><p><bold>Competing Interests: </bold>This work was supported by the National Heart Foundation of Australia, the National Health and Medical Research Council of Australia [APP1029754 and APP472672] and the OIS Program of the Victorian Government, Australia. The Alfred Hospital received funding for Professor Hoy to perform research unrelated to the current manuscript from Merck Sharp & Dohme and Gilead in 2009. No funding was received from commercial funders for this research project. Jennifer F. Hoy has no financial or non-financial competing interests related to the research described in this manuscript. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.</p></fn><fn fn-type="con"><p>Conceived and designed the experiments: JFH PJM. Performed the experiments: JMT BF MC JMW. Analyzed the data: GW JMT JFH PJM. Wrote the paper: GW.</p></fn><fn id="fn1" fn-type="current-aff"><label>¤</label><p>Current address: Infectious Diseases Unit, The Alfred Hospital, Melbourne, Victoria, Australia</p></fn></author-notes><pub-date pub-type="collection"><year>2014</year></pub-date><pub-date pub-type="epub"><day>14</day><month>4</month><year>2014</year></pub-date><volume>9</volume><issue>4</issue><elocation-id>e94810</elocation-id><history><date date-type="received"><day>8</day><month>1</month><year>2014</year></date><date date-type="accepted"><day>20</day><month>3</month><year>2014</year></date></history><permissions><copyright-year>2014</copyright-year><copyright-holder>Wong et al</copyright-holder><license><license-p>This is an open-access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</ext-link>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p></license></permissions><abstract><sec><title>Background</title><p>The increased risk of coronary artery disease in human immunodeficiency virus (HIV) positive patients is collectively contributed to by the human immunodeficiency virus and antiretroviral-associated dyslipidaemia. In this study, we investigate the characterisation of the plasma lipid profiles of treated HIV patients and the relationship of 316 plasma lipid species across multiple lipid classes with the risk of future cardiovascular events in HIV- positive patients.</p></sec><sec><title>Methods</title><p>In a retrospective case-control study, we analysed plasma lipid profiles of 113 subjects. Cases (n = 23) were HIV-positive individuals with a stored blood sample available 12 months prior to their diagnosis of coronary artery disease (CAD). They were age and sex matched to HIV-positive individuals without a diagnosis of CAD (n = 45) and with healthy HIV-negative volunteers (n = 45).</p></sec><sec><title>Results</title><p>Association of plasma lipid species and classes with HIV infection and cardiovascular risk in HIV were determined. In multiple logistic regression, we identified 83 lipids species and 7 lipid classes significantly associated with HIV infection and a further identified 74 lipid species and 8 lipid classes significantly associated with future cardiovascular events in HIV-positive subjects. Risk prediction models incorporating lipid species attained an area under the receiver operator characteristic curve (AUC) of 0.78 (0.775, 0.785)) and outperformed all other tested markers and risk scores in the identification of HIV-positive subjects with increased risk of cardiovascular events.</p></sec><sec><title>Conclusions</title><p>Our results demonstrate that HIV-positive patients have significant differences in their plasma lipid profiles compared with healthy HIV-negative controls and that numerous lipid species were significantly associated with elevated cardiovascular risk. This suggests a potential novel application for plasma lipids in cardiovascular risk screening of HIV-positive patients.</p></sec></abstract><funding-group><funding-statement>This work was supported by the National Heart Foundation of Australia, the National Health and Medical Research Council of Australia [APP1029754 and APP472672] and the OIS Program of the Victorian Government, Australia. The Alfred Hospital received funding for Professor Hoy to perform research unrelated to the current manuscript from Merck Sharp & Dohme and Gilead in 2009. No funding was received from commercial funders for this research project. Jennifer F. Hoy has no financial or non-financial competing interests related to the research described in this manuscript. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.</funding-statement></funding-group><counts><page-count count="7"></page-count></counts></article-meta></front></pmc><affiliations><list><country><li>Australie</li></country></list><tree><country name="Australie"><noRegion><name sortKey="Wong, Gerard" sort="Wong, Gerard" uniqKey="Wong G" first="Gerard" last="Wong">Gerard Wong</name></noRegion><name sortKey="Cinel, Michelle" sort="Cinel, Michelle" uniqKey="Cinel M" first="Michelle" last="Cinel">Michelle Cinel</name><name sortKey="Fatou, Benoit" sort="Fatou, Benoit" uniqKey="Fatou B" first="Benoit" last="Fatou">Benoit Fatou</name><name sortKey="Hoy, Jennifer F" sort="Hoy, Jennifer F" uniqKey="Hoy J" first="Jennifer F." last="Hoy">Jennifer F. Hoy</name><name sortKey="Hoy, Jennifer F" sort="Hoy, Jennifer F" uniqKey="Hoy J" first="Jennifer F." last="Hoy">Jennifer F. Hoy</name><name sortKey="Meikle, Peter J" sort="Meikle, Peter J" uniqKey="Meikle P" first="Peter J." last="Meikle">Peter J. Meikle</name><name sortKey="Trevillyan, Janine M" sort="Trevillyan, Janine M" uniqKey="Trevillyan J" first="Janine M." last="Trevillyan">Janine M. Trevillyan</name><name sortKey="Trevillyan, Janine M" sort="Trevillyan, Janine M" uniqKey="Trevillyan J" first="Janine M." last="Trevillyan">Janine M. Trevillyan</name><name sortKey="Weir, Jacquelyn M" sort="Weir, Jacquelyn M" uniqKey="Weir J" first="Jacquelyn M." last="Weir">Jacquelyn M. Weir</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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