Effects of ARVs and HIV on mitochondrial function and immune activation in monocyte derived macrophages in vitro

While ART reduces HIV associated morbidity and mortality, low levels of persistent inflammation in virally suppressed individuals drive a form of accelerated aging and comorbidity. Macrophage activation drives persistent inflammation but the molecular mechanisms remain poorly understood. Uninfected and HIV-infected MDMs were treated with ARVs: TFV, 3TC, and EFV, and alterations in cell viability and mitochondrial function were characterized. Alterations were then examined for effects on inflammatory cytokine production. ARV treatment had distinct effects on mitochondrial function and metabolism. TFV increased cellular ROS, decreased cellular respiration, increased cell death, and decreased TNF-alpha. EFV decreased cellular respiration, decreased ATP production, decreased expression of complex I of the ETC, increased cell death, increased superoxide and cellular ROS, and increased TNF-alpha and IFN-beta production. In the context of HIV infection, TFV and EFV, increased cellular ROS production and TFV also decreased complex I expression of the ETC.

Name thesis:degree_name

Master of Science (M.Sc.)

Level thesis:degree_level

Master's

Discipline thesis:degree_discipline

Health Sciences

Grantor dc:publisher

Carleton University

Year dc:date.issued

2019

Author dc:creator

• Roy, David

Statement dc:rights

• Copyright © 2019 the author(s). Theses may be used for non-commercial research, educational, or related academic purposes only. Such uses include personal study, research, scholarship, and teaching. Theses may only be shared by linking to Carleton University Institutional Repository and no part may be used without proper attribution to the author. No part may be used for commercial purposes directly or indirectly via a for-profit platform; no adaptation or derivative works are permitted without consent from the copyright owner.

Language dc:language.iso

en

DOI

10.22215/etd/2019-13752

OAI identifier oai:identifier

oai:carleton.scholaris.ca:20.500.14718/40365