Improved adipose tissue function with initiation of protease inhibitor-only ART
Identifieur interne : 003982 ( Ncbi/Curation ); précédent : 003981; suivant : 003983Improved 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.
Descripteurs français
- KwdFr :
- ADN mitochondrial (analyse), Adulte, Analyse de profil d'expression de gènes, Biopsie, Femelle, Graisse sous-cutanée (), Graisse sous-cutanée (physiologie), Histocytochimie, Humains, Infections à VIH (traitement médicamenteux), Inhibiteurs de protéase du VIH (effets indésirables), Inhibiteurs de protéase du VIH (usage thérapeutique), Mâle, Protéome (analyse), Thaïlande.
- MESH :
- analyse : ADN mitochondrial, Protéome.
- effets indésirables : Inhibiteurs de protéase du VIH.
- physiologie : Graisse sous-cutanée.
- traitement médicamenteux : Infections à VIH.
- usage thérapeutique : Inhibiteurs de protéase du VIH.
- Adulte, Analyse de profil d'expression de gènes, Biopsie, Femelle, Graisse sous-cutanée, Histocytochimie, Humains, Mâle, Thaïlande.
English descriptors
- KwdEn :
- Adult, Biopsy, DNA, Mitochondrial (analysis), Female, Gene Expression Profiling, HIV Infections (drug therapy), HIV Protease Inhibitors (adverse effects), HIV Protease Inhibitors (therapeutic use), Histocytochemistry, Humans, Male, Proteome (analysis), Subcutaneous Fat (drug effects), Subcutaneous Fat (physiology), Thailand.
- MESH :
- chemical , adverse effects : HIV Protease Inhibitors.
- chemical , analysis : DNA, Mitochondrial, Proteome.
- drug effects : Subcutaneous Fat.
- drug therapy : HIV Infections.
- physiology : Subcutaneous Fat.
- chemical , therapeutic use : HIV Protease Inhibitors.
- Adult, Biopsy, Female, Gene Expression Profiling, Histocytochemistry, Humans, Male, Thailand.
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
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PMC:5079304Le document en format XML
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Improved adipose tissue function with initiation of protease inhibitor-only ART</title>
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<author><name sortKey="Domingo, Pere" sort="Domingo, Pere" uniqKey="Domingo P" first="Pere" last="Domingo">Pere Domingo</name>
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</nlm:aff>
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<author><name sortKey="Giralt, Marta" sort="Giralt, Marta" uniqKey="Giralt M" first="Marta" last="Giralt">Marta Giralt</name>
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</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<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>
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,<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>
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,<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>
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<author><name sortKey="Phanuphak, Praphan" sort="Phanuphak, Praphan" uniqKey="Phanuphak P" first="Praphan" last="Phanuphak">Praphan Phanuphak</name>
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</nlm:aff>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<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>
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<author><name sortKey="Cooper, David A" sort="Cooper, David A" uniqKey="Cooper D" first="David A." last="Cooper">David A. Cooper</name>
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</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Reiss, Peter" sort="Reiss, Peter" uniqKey="Reiss P" first="Peter" last="Reiss">Peter Reiss</name>
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,<institution>and Amsterdam Institute for Global Health and Development</institution>
,<addr-line>Amsterdam</addr-line>
,<country>The Netherlands</country>
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<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>
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,<country>Ireland</country>
</nlm:aff>
<country xml:lang="fr">Irlande (pays)</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term>
<term>Biopsy</term>
<term>DNA, Mitochondrial (analysis)</term>
<term>Female</term>
<term>Gene Expression Profiling</term>
<term>HIV Infections (drug therapy)</term>
<term>HIV Protease Inhibitors (adverse effects)</term>
<term>HIV Protease Inhibitors (therapeutic use)</term>
<term>Histocytochemistry</term>
<term>Humans</term>
<term>Male</term>
<term>Proteome (analysis)</term>
<term>Subcutaneous Fat (drug effects)</term>
<term>Subcutaneous Fat (physiology)</term>
<term>Thailand</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>ADN mitochondrial (analyse)</term>
<term>Adulte</term>
<term>Analyse de profil d'expression de gènes</term>
<term>Biopsie</term>
<term>Femelle</term>
<term>Graisse sous-cutanée ()</term>
<term>Graisse sous-cutanée (physiologie)</term>
<term>Histocytochimie</term>
<term>Humains</term>
<term>Infections à VIH (traitement médicamenteux)</term>
<term>Inhibiteurs de protéase du VIH (effets indésirables)</term>
<term>Inhibiteurs de protéase du VIH (usage thérapeutique)</term>
<term>Mâle</term>
<term>Protéome (analyse)</term>
<term>Thaïlande</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>HIV Protease Inhibitors</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>DNA, Mitochondrial</term>
<term>Proteome</term>
</keywords>
<keywords scheme="MESH" qualifier="analyse" xml:lang="fr"><term>ADN mitochondrial</term>
<term>Protéome</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Subcutaneous Fat</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>HIV Infections</term>
</keywords>
<keywords scheme="MESH" qualifier="effets indésirables" xml:lang="fr"><term>Inhibiteurs de protéase du VIH</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Graisse sous-cutanée</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Subcutaneous Fat</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>HIV Protease Inhibitors</term>
</keywords>
<keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Infections à VIH</term>
</keywords>
<keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Inhibiteurs de protéase du VIH</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adult</term>
<term>Biopsy</term>
<term>Female</term>
<term>Gene Expression Profiling</term>
<term>Histocytochemistry</term>
<term>Humans</term>
<term>Male</term>
<term>Thailand</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Adulte</term>
<term>Analyse de profil d'expression de gènes</term>
<term>Biopsie</term>
<term>Femelle</term>
<term>Graisse sous-cutanée</term>
<term>Histocytochimie</term>
<term>Humains</term>
<term>Mâle</term>
<term>Thaïlande</term>
</keywords>
</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>
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