Improved adipose tissue function with initiation of protease inhibitor-only ART
Maughan, Robert T. (University College Dublin)
Feeney, Eoin R. (University College Dublin)
Capel, Emilie (Sorbonne Universities)
Capeau, Jacqueline (Sorbonne Universities)
Domingo, Pere (Institut d'Investigació Biomèdica Sant Pau)
Giralt, Marta (CIBER Fisiopatologia de la Obesidad y Nutrición)
Lange, Joep M.A. (Thai Red Cross Aids Research Center (TRCARC))
Phanuphak, Praphan (Chulalongkorn University)
Cooper, David A. (University of New South Wales)
Reiss, Peter (Thai Red Cross Aids Research Center (TRCARC))
Mallon, Patrick W.G. (University College Dublin)
Autar, Saskia R.
van der Lugt, Jasper
Avihingsanon, Anchalee
Klungklang, Supalak
Ubolyam, Sasiwimol
Universitat Autònoma de Barcelona

Fecha:	2016
Resumen:	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, P = 0. 023), coinciding with larger adipocytes as indicated by decreased adipocyte density in biopsies (-32. 3 cells/mm, P = 0. 047) and increased mRNA expression of adipogenesis regulator PPARG at week 2 (+58. 1%, P = 0. 003). Increases in mtDNA over 24 weeks (+600 copies/cell, P = 0. 041), decreased NRF1 mRNA expression at week 2 (-33. 7%, P < 0. 001) and increased COX2/COX4 protein ratio at week 24 (+288%, P = 0. 038) indicated improved mitochondrial function. Despite decreased AKT2 mRNA at week 2 (-28. 6%, P = 0. 002) and increased PTPN1 mRNA at week 24 (+50. 3%, P = 0. 016) suggesting insulin resistance, clinical insulin sensitivity [by homeostasis model assessment (HOMA-IR)] was unchanged. 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.
Ayudas:	Ministerio de Economía y Competitividad PI14/00700 Ministerio de Economía y Competitividad PI14/00063
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Publicado en:	Journal of antimicrobial chemotherapy, Vol. 71 Núm. 11 (january 2016) , p. 3212-3221, ISSN 1460-2091

DOI: 10.1093/jac/dkw301
PMID: 27516476

10 p, 482.9 KB

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