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J Antimicrob Chemother. 2016 Nov;71(11):3212-3221. Epub 2016 Aug 11.

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

Author information

1
HIV Molecular Research Group, School of Medicine, University College Dublin, Dublin, Ireland robert.maughan@ucdconnect.ie.
2
HIV Molecular Research Group, School of Medicine, University College Dublin, Dublin, Ireland.
3
Sorbonne Universities, UPMC Univ Paris 06, INSERM UMRS 938, Paris, France.
4
Infectious Diseases Unit, Hospital de la Santa Creu/Sant Pau, Barcelona, Spain.
5
Department of Biochemistry and Molecular Biology, University of Barcelona, Barcelona, Spain.
6
CIBER Fisiopatologia de la Obesidad y Nutrición, Barcelona, Spain.
7
Academic Medical Center, Department of Global Health and Division of Infectious Diseases, and Amsterdam Institute for Global Health and Development, Amsterdam, The Netherlands.
8
The HIV-Netherlands Australia Thailand Research Collaboration (HIV-NAT) - Thai Red Cross Aids Research Center (TRCARC), Bangkok, Thailand.
9
Department of Medicine, Chulalongkorn University, Bangkok, Thailand.
10
Kirby Institute, University of New South Wales, Sydney, Australia.

Abstract

OBJECTIVES:

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.

METHODS:

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.

RESULTS:

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 < 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.

CONCLUSIONS:

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.

PMID:
27516476
PMCID:
PMC5079304
DOI:
10.1093/jac/dkw301
[Indexed for MEDLINE]
Free PMC Article

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