Improved adipose tissue function with initiation of protease inhibitor-only ART
Identifieur interne : 000846 ( Pmc/Checkpoint ); précédent : 000845; suivant : 000847Improved adipose tissue function with initiation of protease inhibitor-only ART
Auteurs : Robert T. Maughan [Irlande (pays)] ; Eoin R. Feeney [Irlande (pays)] ; Emilie Capel [France] ; Jacqueline Capeau [France] ; Pere Domingo [Espagne] ; Marta Giralt [Espagne] ; Joep M. A. Lange [Pays-Bas, Thaïlande] ; Praphan Phanuphak [Thaïlande] ; David A. Cooper [Australie] ; Peter Reiss [Pays-Bas, Thaïlande] ; Patrick W. G. Mallon [Irlande (pays)]Source :
- Journal of Antimicrobial Chemotherapy [ 0305-7453 ] ; 2016.
Abstract
Use of ART containing HIV PIs has previously been associated with toxicity in subcutaneous adipose tissue (SAT), potentially contributing to the development of lipodystrophy and insulin resistance. However, the effect of PIs on SAT function in ART-naive patients independent of other ART classes is unknown. This study aimed to elucidate the effect of initiating PI-only ART on SAT function in ART-naive subjects.
In the HIVNAT-019 study, 48 HIV-infected, ART-naive Thai adults commencing PI-only ART comprising lopinavir/ritonavir/saquinavir for 24 weeks underwent assessments of fasting metabolic parameters and body composition. In a molecular substudy, 20 subjects underwent SAT biopsies at weeks 0, 2 and 24 for transcriptional, protein, mitochondrial DNA (mtDNA) and histological analyses. ClinicalTrials.gov registration number: NCT00400738.
Over 24 weeks, limb fat increased (+416.4 g,
Initiation of PI-only ART showed little evidence of SAT toxicity, the changes observed being consistent with a return to health rather than contributing to lipodystrophy.
Url:
DOI: 10.1093/jac/dkw301
PubMed: 27516476
PubMed Central: 5079304
Affiliations:
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A." last="Lange">Joep M. A. Lange</name><affiliation wicri:level="1"><nlm:aff id="af6"><addr-line>Academic Medical Center, Department of Global Health and Division of Infectious Diseases</addr-line>,<institution>and Amsterdam Institute for Global Health and Development</institution>,<addr-line>Amsterdam</addr-line>,<country>The Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af7"><institution>The HIV-Netherlands Australia Thailand Research Collaboration (HIV-NAT) - Thai Red Cross Aids Research Center (TRCARC)</institution>,<addr-line>Bangkok</addr-line>,<country>Thailand</country></nlm:aff><country xml:lang="fr">Thaïlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Phanuphak, Praphan" sort="Phanuphak, Praphan" uniqKey="Phanuphak P" first="Praphan" last="Phanuphak">Praphan Phanuphak</name><affiliation wicri:level="1"><nlm:aff id="af7"><institution>The HIV-Netherlands Australia Thailand Research Collaboration (HIV-NAT) - Thai Red Cross Aids Research Center (TRCARC)</institution>,<addr-line>Bangkok</addr-line>,<country>Thailand</country></nlm:aff><country xml:lang="fr">Thaïlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af8"><institution>Department of Medicine, Chulalongkorn University</institution>,<addr-line>Bangkok</addr-line>,<country>Thailand</country></nlm:aff><country xml:lang="fr">Thaïlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Cooper, David A" sort="Cooper, David A" uniqKey="Cooper D" first="David A." last="Cooper">David A. Cooper</name><affiliation wicri:level="1"><nlm:aff id="af9"><institution>Kirby Institute</institution>,<institution>University of New South Wales</institution>,<addr-line>Sydney</addr-line>,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Reiss, Peter" sort="Reiss, Peter" uniqKey="Reiss P" first="Peter" last="Reiss">Peter Reiss</name><affiliation wicri:level="1"><nlm:aff id="af6"><addr-line>Academic Medical Center, Department of Global Health and Division of Infectious Diseases</addr-line>,<institution>and Amsterdam Institute for Global Health and Development</institution>,<addr-line>Amsterdam</addr-line>,<country>The Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af7"><institution>The HIV-Netherlands Australia Thailand Research Collaboration (HIV-NAT) - Thai Red Cross Aids Research Center (TRCARC)</institution>,<addr-line>Bangkok</addr-line>,<country>Thailand</country></nlm:aff><country xml:lang="fr">Thaïlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Mallon, Patrick W G" sort="Mallon, Patrick W G" uniqKey="Mallon P" first="Patrick W. G." last="Mallon">Patrick W. G. Mallon</name><affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>HIV Molecular Research Group, School of Medicine</addr-line>,<institution>University College Dublin</institution>,<addr-line>Dublin</addr-line>,<country>Ireland</country></nlm:aff><country xml:lang="fr">Irlande (pays)</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27516476</idno><idno type="pmc">5079304</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5079304</idno><idno type="RBID">PMC:5079304</idno><idno type="doi">10.1093/jac/dkw301</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">002628</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002628</idno><idno type="wicri:Area/Pmc/Curation">002478</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">002478</idno><idno type="wicri:Area/Pmc/Checkpoint">000846</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000846</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Improved adipose tissue function with initiation of protease inhibitor-only ART</title><author><name sortKey="Maughan, Robert T" sort="Maughan, Robert T" uniqKey="Maughan R" first="Robert T." last="Maughan">Robert T. Maughan</name><affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>HIV Molecular Research Group, School of Medicine</addr-line>,<institution>University College Dublin</institution>,<addr-line>Dublin</addr-line>,<country>Ireland</country></nlm:aff><country xml:lang="fr">Irlande (pays)</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Feeney, Eoin R" sort="Feeney, Eoin R" uniqKey="Feeney E" first="Eoin R." last="Feeney">Eoin R. Feeney</name><affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>HIV Molecular Research Group, School of Medicine</addr-line>,<institution>University College Dublin</institution>,<addr-line>Dublin</addr-line>,<country>Ireland</country></nlm:aff><country xml:lang="fr">Irlande (pays)</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Capel, Emilie" sort="Capel, Emilie" uniqKey="Capel E" first="Emilie" last="Capel">Emilie Capel</name><affiliation wicri:level="1"><nlm:aff id="af2"><institution>Sorbonne Universities, UPMC Univ Paris 06, INSERM UMRS 938</institution>,<addr-line>Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Capeau, Jacqueline" sort="Capeau, Jacqueline" uniqKey="Capeau J" first="Jacqueline" last="Capeau">Jacqueline Capeau</name><affiliation wicri:level="1"><nlm:aff id="af2"><institution>Sorbonne Universities, UPMC Univ Paris 06, INSERM UMRS 938</institution>,<addr-line>Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Domingo, Pere" sort="Domingo, Pere" uniqKey="Domingo P" first="Pere" last="Domingo">Pere Domingo</name><affiliation wicri:level="1"><nlm:aff id="af3"><institution>Infectious Diseases Unit, Hospital de la Santa Creu/Sant Pau</institution>,<addr-line>Barcelona</addr-line>,<country>Spain</country></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Giralt, Marta" sort="Giralt, Marta" uniqKey="Giralt M" first="Marta" last="Giralt">Marta Giralt</name><affiliation wicri:level="1"><nlm:aff id="af4"><addr-line>Department of Biochemistry and Molecular Biology</addr-line>,<institution>University of Barcelona</institution>,<addr-line>Barcelona</addr-line>,<country>Spain</country></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af5"><institution>CIBER Fisiopatologia de la Obesidad y Nutrición</institution>,<addr-line>Barcelona, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Barcelona</wicri:regionArea></affiliation></author><author><name sortKey="Lange, Joep M A" sort="Lange, Joep M A" uniqKey="Lange J" first="Joep M. A." last="Lange">Joep M. A. Lange</name><affiliation wicri:level="1"><nlm:aff id="af6"><addr-line>Academic Medical Center, Department of Global Health and Division of Infectious Diseases</addr-line>,<institution>and Amsterdam Institute for Global Health and Development</institution>,<addr-line>Amsterdam</addr-line>,<country>The Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af7"><institution>The HIV-Netherlands Australia Thailand Research Collaboration (HIV-NAT) - Thai Red Cross Aids Research Center (TRCARC)</institution>,<addr-line>Bangkok</addr-line>,<country>Thailand</country></nlm:aff><country xml:lang="fr">Thaïlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Phanuphak, Praphan" sort="Phanuphak, Praphan" uniqKey="Phanuphak P" first="Praphan" last="Phanuphak">Praphan Phanuphak</name><affiliation wicri:level="1"><nlm:aff id="af7"><institution>The HIV-Netherlands Australia Thailand Research Collaboration (HIV-NAT) - Thai Red Cross Aids Research Center (TRCARC)</institution>,<addr-line>Bangkok</addr-line>,<country>Thailand</country></nlm:aff><country xml:lang="fr">Thaïlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af8"><institution>Department of Medicine, Chulalongkorn University</institution>,<addr-line>Bangkok</addr-line>,<country>Thailand</country></nlm:aff><country xml:lang="fr">Thaïlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Cooper, David A" sort="Cooper, David A" uniqKey="Cooper D" first="David A." last="Cooper">David A. Cooper</name><affiliation wicri:level="1"><nlm:aff id="af9"><institution>Kirby Institute</institution>,<institution>University of New South Wales</institution>,<addr-line>Sydney</addr-line>,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Reiss, Peter" sort="Reiss, Peter" uniqKey="Reiss P" first="Peter" last="Reiss">Peter Reiss</name><affiliation wicri:level="1"><nlm:aff id="af6"><addr-line>Academic Medical Center, Department of Global Health and Division of Infectious Diseases</addr-line>,<institution>and Amsterdam Institute for Global Health and Development</institution>,<addr-line>Amsterdam</addr-line>,<country>The Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af7"><institution>The HIV-Netherlands Australia Thailand Research Collaboration (HIV-NAT) - Thai Red Cross Aids Research Center (TRCARC)</institution>,<addr-line>Bangkok</addr-line>,<country>Thailand</country></nlm:aff><country xml:lang="fr">Thaïlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Mallon, Patrick W G" sort="Mallon, Patrick W G" uniqKey="Mallon P" first="Patrick W. G." last="Mallon">Patrick W. G. Mallon</name><affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>HIV Molecular Research Group, School of Medicine</addr-line>,<institution>University College Dublin</institution>,<addr-line>Dublin</addr-line>,<country>Ireland</country></nlm:aff><country xml:lang="fr">Irlande (pays)</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Journal of Antimicrobial Chemotherapy</title><idno type="ISSN">0305-7453</idno><idno type="eISSN">1460-2091</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Objectives</title><p>Use of ART containing HIV PIs has previously been associated with toxicity in subcutaneous adipose tissue (SAT), potentially contributing to the development of lipodystrophy and insulin resistance. However, the effect of PIs on SAT function in ART-naive patients independent of other ART classes is unknown. This study aimed to elucidate the effect of initiating PI-only ART on SAT function in ART-naive subjects.</p></sec><sec><title>Methods</title><p>In the HIVNAT-019 study, 48 HIV-infected, ART-naive Thai adults commencing PI-only ART comprising lopinavir/ritonavir/saquinavir for 24 weeks underwent assessments of fasting metabolic parameters and body composition. In a molecular substudy, 20 subjects underwent SAT biopsies at weeks 0, 2 and 24 for transcriptional, protein, mitochondrial DNA (mtDNA) and histological analyses. ClinicalTrials.gov registration number: NCT00400738.</p></sec><sec><title>Results</title><p>Over 24 weeks, limb fat increased (+416.4 g, <italic>P </italic>= 0.023), coinciding with larger adipocytes as indicated by decreased adipocyte density in biopsies (−32.3 cells/mm<sup>2</sup>, <italic>P </italic>= 0.047) and increased mRNA expression of adipogenesis regulator <italic>PPARG</italic> at week 2 (+58.1%, <italic>P </italic>= 0.003). Increases in mtDNA over 24 weeks (+600 copies/cell, <italic>P </italic>= 0.041), decreased <italic>NRF1</italic> mRNA expression at week 2 (−33.7%, <italic>P </italic>< 0.001) and increased COX2/COX4 protein ratio at week 24 (+288%, <italic>P </italic>= 0.038) indicated improved mitochondrial function. Despite decreased <italic>AKT2</italic> mRNA at week 2 (−28.6%, <italic>P </italic>= 0.002) and increased <italic>PTPN1</italic> mRNA at week 24 (+50.3%, <italic>P </italic>= 0.016) suggesting insulin resistance, clinical insulin sensitivity [by homeostasis model assessment (HOMA-IR)] was unchanged.</p></sec><sec><title>Conclusions</title><p>Initiation of PI-only ART showed little evidence of SAT toxicity, the changes observed being consistent with a return to health rather than contributing to lipodystrophy.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Lake, Je" uniqKey="Lake J">JE Lake</name></author><author><name sortKey="Currier, Js" uniqKey="Currier J">JS Currier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rodger, Aj" uniqKey="Rodger A">AJ Rodger</name></author><author><name sortKey="Lodwick, R" uniqKey="Lodwick R">R Lodwick</name></author><author><name sortKey="Schechter, M" 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<front><journal-meta><journal-id journal-id-type="nlm-ta">J Antimicrob Chemother</journal-id><journal-id journal-id-type="iso-abbrev">J. Antimicrob. Chemother</journal-id><journal-id journal-id-type="publisher-id">jac</journal-id><journal-id journal-id-type="hwp">jac</journal-id><journal-title-group><journal-title>Journal of Antimicrobial Chemotherapy</journal-title></journal-title-group><issn pub-type="ppub">0305-7453</issn><issn pub-type="epub">1460-2091</issn><publisher><publisher-name>Oxford University Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">27516476</article-id><article-id pub-id-type="pmc">5079304</article-id><article-id pub-id-type="doi">10.1093/jac/dkw301</article-id><article-id pub-id-type="publisher-id">dkw301</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Research</subject></subj-group></article-categories><title-group><article-title>Improved adipose tissue function with initiation of protease inhibitor-only ART</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Maughan</surname><given-names>Robert T.</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="corresp" rid="cor1">*</xref></contrib><contrib contrib-type="author"><name><surname>Feeney</surname><given-names>Eoin R.</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Capel</surname><given-names>Emilie</given-names></name><xref ref-type="aff" rid="af2">2</xref></contrib><contrib contrib-type="author"><name><surname>Capeau</surname><given-names>Jacqueline</given-names></name><xref ref-type="aff" rid="af2">2</xref></contrib><contrib contrib-type="author"><name><surname>Domingo</surname><given-names>Pere</given-names></name><xref ref-type="aff" rid="af3">3</xref></contrib><contrib contrib-type="author"><name><surname>Giralt</surname><given-names>Marta</given-names></name><xref ref-type="aff" rid="af4">4</xref><xref ref-type="aff" rid="af5">5</xref></contrib><contrib contrib-type="author"><name><surname>Lange</surname><given-names>Joep M. A.</given-names></name><xref ref-type="aff" rid="af6">6</xref><xref ref-type="aff" rid="af7">7</xref><xref ref-type="author-notes" rid="FN1">†</xref></contrib><contrib contrib-type="author"><name><surname>Phanuphak</surname><given-names>Praphan</given-names></name><xref ref-type="aff" rid="af7">7</xref><xref ref-type="aff" rid="af8">8</xref></contrib><contrib contrib-type="author"><name><surname>Cooper</surname><given-names>David A.</given-names></name><xref ref-type="aff" rid="af9">9</xref></contrib><contrib contrib-type="author"><name><surname>Reiss</surname><given-names>Peter</given-names></name><xref ref-type="aff" rid="af6">6</xref><xref ref-type="aff" rid="af7">7</xref></contrib><contrib contrib-type="author"><name><surname>Mallon</surname><given-names>Patrick W. G.</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><on-behalf-of>on behalf of the HIVNAT-019 Study Group</on-behalf-of><xref ref-type="author-notes" rid="FN2">‡</xref><aff id="af1"><label>1</label><addr-line>HIV Molecular Research Group, School of Medicine</addr-line>,<institution>University College Dublin</institution>,<addr-line>Dublin</addr-line>,<country>Ireland</country></aff><aff id="af2"><label>2</label><institution>Sorbonne Universities, UPMC Univ Paris 06, INSERM UMRS 938</institution>,<addr-line>Paris</addr-line>,<country>France</country></aff><aff id="af3"><label>3</label><institution>Infectious Diseases Unit, Hospital de la Santa Creu/Sant Pau</institution>,<addr-line>Barcelona</addr-line>,<country>Spain</country></aff><aff id="af4"><label>4</label><addr-line>Department of Biochemistry and Molecular Biology</addr-line>,<institution>University of Barcelona</institution>,<addr-line>Barcelona</addr-line>,<country>Spain</country></aff><aff id="af5"><label>5</label><institution>CIBER Fisiopatologia de la Obesidad y Nutrición</institution>,<addr-line>Barcelona, Spain</addr-line></aff><aff id="af6"><label>6</label><addr-line>Academic Medical Center, Department of Global Health and Division of Infectious Diseases</addr-line>,<institution>and Amsterdam Institute for Global Health and Development</institution>,<addr-line>Amsterdam</addr-line>,<country>The Netherlands</country></aff><aff id="af7"><label>7</label><institution>The HIV-Netherlands Australia Thailand Research Collaboration (HIV-NAT) - Thai Red Cross Aids Research Center (TRCARC)</institution>,<addr-line>Bangkok</addr-line>,<country>Thailand</country></aff><aff id="af8"><label>8</label><institution>Department of Medicine, Chulalongkorn University</institution>,<addr-line>Bangkok</addr-line>,<country>Thailand</country></aff><aff id="af9"><label>9</label><institution>Kirby Institute</institution>,<institution>University of New South Wales</institution>,<addr-line>Sydney</addr-line>,<country>Australia</country></aff></contrib-group><contrib-group><contrib contrib-type="collab"><collab>on behalf of the HIVNAT-019 Study Group</collab></contrib><contrib contrib-type="collab"><name><surname>Autar</surname><given-names>Saskia R.</given-names></name></contrib><contrib contrib-type="collab"><name><surname>van der Lugt</surname><given-names>Jasper</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Avihingsanon</surname><given-names>Anchalee</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Klungklang</surname><given-names>Supalak</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Ubolyam</surname><given-names>Sasiwimol</given-names></name></contrib></contrib-group><author-notes><corresp id="cor1"><label>*</label>Corresponding author. Tel: +<phone>353-1-716-4584</phone>; Fax: +<fax>353-1-716-4539</fax>; E-mail: <email>robert.maughan@ucdconnect.ie</email></corresp><fn id="FN1" fn-type="con"><label>†</label><p>Deceased 17 July 2014.</p></fn><fn id="FN2" fn-type="con"><label>‡</label><p>Additional members of the HIVNAT-019 Study Group are listed in the Acknowledgements section.</p></fn></author-notes><pub-date pub-type="ppub"><month>11</month><year>2016</year></pub-date><pub-date pub-type="epub"><day>11</day><month>8</month><year>2016</year></pub-date><pub-date pub-type="pmc-release"><day>11</day><month>8</month><year>2016</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
<volume>71</volume><issue>11</issue><fpage>3212</fpage><lpage>3221</lpage><history><date date-type="received"><day>22</day><month>4</month><year>2016</year></date><date date-type="accepted"><day>27</day><month>6</month><year>2016</year></date></history><permissions><copyright-statement>© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.</copyright-statement><copyright-year>2016</copyright-year><license license-type="creative-commons" xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions><self-uri content-type="pdf" xlink:href="dkw301.pdf"></self-uri><abstract><sec><title>Objectives</title><p>Use of ART containing HIV PIs has previously been associated with toxicity in subcutaneous adipose tissue (SAT), potentially contributing to the development of lipodystrophy and insulin resistance. However, the effect of PIs on SAT function in ART-naive patients independent of other ART classes is unknown. This study aimed to elucidate the effect of initiating PI-only ART on SAT function in ART-naive subjects.</p></sec><sec><title>Methods</title><p>In the HIVNAT-019 study, 48 HIV-infected, ART-naive Thai adults commencing PI-only ART comprising lopinavir/ritonavir/saquinavir for 24 weeks underwent assessments of fasting metabolic parameters and body composition. In a molecular substudy, 20 subjects underwent SAT biopsies at weeks 0, 2 and 24 for transcriptional, protein, mitochondrial DNA (mtDNA) and histological analyses. ClinicalTrials.gov registration number: NCT00400738.</p></sec><sec><title>Results</title><p>Over 24 weeks, limb fat increased (+416.4 g, <italic>P </italic>= 0.023), coinciding with larger adipocytes as indicated by decreased adipocyte density in biopsies (−32.3 cells/mm<sup>2</sup>, <italic>P </italic>= 0.047) and increased mRNA expression of adipogenesis regulator <italic>PPARG</italic> at week 2 (+58.1%, <italic>P </italic>= 0.003). Increases in mtDNA over 24 weeks (+600 copies/cell, <italic>P </italic>= 0.041), decreased <italic>NRF1</italic> mRNA expression at week 2 (−33.7%, <italic>P </italic>< 0.001) and increased COX2/COX4 protein ratio at week 24 (+288%, <italic>P </italic>= 0.038) indicated improved mitochondrial function. Despite decreased <italic>AKT2</italic> mRNA at week 2 (−28.6%, <italic>P </italic>= 0.002) and increased <italic>PTPN1</italic> mRNA at week 24 (+50.3%, <italic>P </italic>= 0.016) suggesting insulin resistance, clinical insulin sensitivity [by homeostasis model assessment (HOMA-IR)] was unchanged.</p></sec><sec><title>Conclusions</title><p>Initiation of PI-only ART showed little evidence of SAT toxicity, the changes observed being consistent with a return to health rather than contributing to lipodystrophy.</p></sec></abstract><funding-group><award-group id="funding-1"><funding-source><institution-wrap><institution>European AIDS Treatment Network</institution></institution-wrap></funding-source><award-id>NEAT IG3</award-id></award-group><award-group id="funding-2"><funding-source><institution-wrap><institution>Wellcome Trust</institution></institution-wrap></funding-source><award-id>097424/Z/11/Z</award-id></award-group><award-group id="funding-3"><funding-source><institution-wrap><institution>Molecular Medicine Ireland; Science Foundation Ireland</institution></institution-wrap></funding-source><award-id>09/RFP/BMT2461</award-id></award-group><award-group id="funding-4"><funding-source><institution-wrap><institution>Roche Pharmaceuticals</institution></institution-wrap></funding-source></award-group></funding-group></article-meta></front></pmc><affiliations><list><country><li>Australie</li><li>Espagne</li><li>France</li><li>Irlande (pays)</li><li>Pays-Bas</li><li>Thaïlande</li></country></list><tree><country name="Irlande (pays)"><noRegion><name sortKey="Maughan, Robert T" sort="Maughan, Robert T" uniqKey="Maughan R" first="Robert T." last="Maughan">Robert T. Maughan</name></noRegion><name sortKey="Feeney, Eoin R" sort="Feeney, Eoin R" uniqKey="Feeney E" first="Eoin R." last="Feeney">Eoin R. Feeney</name><name sortKey="Mallon, Patrick W G" sort="Mallon, Patrick W G" uniqKey="Mallon P" first="Patrick W. G." last="Mallon">Patrick W. G. Mallon</name></country><country name="France"><noRegion><name sortKey="Capel, Emilie" sort="Capel, Emilie" uniqKey="Capel E" first="Emilie" last="Capel">Emilie Capel</name></noRegion><name sortKey="Capeau, Jacqueline" sort="Capeau, Jacqueline" uniqKey="Capeau J" first="Jacqueline" last="Capeau">Jacqueline Capeau</name></country><country name="Espagne"><noRegion><name sortKey="Domingo, Pere" sort="Domingo, Pere" uniqKey="Domingo P" first="Pere" last="Domingo">Pere Domingo</name></noRegion><name sortKey="Giralt, Marta" sort="Giralt, Marta" uniqKey="Giralt M" first="Marta" last="Giralt">Marta Giralt</name><name sortKey="Giralt, Marta" sort="Giralt, Marta" uniqKey="Giralt M" first="Marta" last="Giralt">Marta Giralt</name></country><country name="Pays-Bas"><noRegion><name sortKey="Lange, Joep M A" sort="Lange, Joep M A" uniqKey="Lange J" first="Joep M. A." last="Lange">Joep M. A. Lange</name></noRegion><name sortKey="Reiss, Peter" sort="Reiss, Peter" uniqKey="Reiss P" first="Peter" last="Reiss">Peter Reiss</name></country><country name="Thaïlande"><noRegion><name sortKey="Lange, Joep M A" sort="Lange, Joep M A" uniqKey="Lange J" first="Joep M. A." last="Lange">Joep M. A. Lange</name></noRegion><name sortKey="Phanuphak, Praphan" sort="Phanuphak, Praphan" uniqKey="Phanuphak P" first="Praphan" last="Phanuphak">Praphan Phanuphak</name><name sortKey="Phanuphak, Praphan" sort="Phanuphak, Praphan" uniqKey="Phanuphak P" first="Praphan" last="Phanuphak">Praphan Phanuphak</name><name sortKey="Reiss, Peter" sort="Reiss, Peter" uniqKey="Reiss P" first="Peter" last="Reiss">Peter Reiss</name></country><country name="Australie"><noRegion><name sortKey="Cooper, David A" sort="Cooper, David A" uniqKey="Cooper D" first="David A." last="Cooper">David A. Cooper</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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