Improved adipose tissue function with initiation of protease inhibitor-only ART.

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, P?=?0.023), coinciding with larger adipocytes as indicated by decreased adipocyte density in biopsies (-32.3 cells/mm2, 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?

SUBMITTER: Maughan RT 

PROVIDER: S-EPMC5079304 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature