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

Robert T. Maughan*, Eoin R. Feeney, Emilie Capel, Jacqueline Capeau, Pere Domingo, Marta Giralt, Joep M.A. Lange, Praphan Phanuphak, David A. Cooper, Peter Reiss, Patrick W.G. Mallon, Saskia R. Autar, Jasper van der Lugt, Anchalee Avihingsanon, Supalak Klungklang, Sasiwimol Ubolyam

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Article numberdkw301
Pages (from-to)3212-3221
Number of pages10
JournalJournal of Antimicrobial Chemotherapy
Volume71
Issue number11
DOIs
Publication statusPublished - 1 Nov 2016

Cite this

Maughan, R. T., Feeney, E. R., Capel, E., Capeau, J., Domingo, P., Giralt, M., ... Ubolyam, S. (2016). Improved adipose tissue function with initiation of protease inhibitor-only ART. Journal of Antimicrobial Chemotherapy, 71(11), 3212-3221. [dkw301]. https://doi.org/10.1093/jac/dkw301