Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 65, Issue 1, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.01755-20
Keywords
preexposure prophylaxis; mitochondrial dysfunction; leukocytes; lipids; inflammation; human immunodeficiency virus
Categories
Funding
- Ohio State University Comprehensive Cancer Center
- National Institutes of Health [R01HL134544]
- National Center for Advancing Translational Sciences
Ask authors/readers for more resources
The study found that exposure of leukocytes to TDF or FTC in the context of PrEP resulted in decreased mitochondrial function and altered functional and transcriptional profiles. These findings may have important implications for the metabolic and immunologic consequences of PrEP in populations at risk for HIV acquisition.
The use of antiretroviral therapy (ART) as preexposure prophylaxis (PrEP) is an effective strategy for preventing HIV acquisition. The cellular consequences of PrEP exposure, however, have not been sufficiently explored to determine potential effects on health in individuals without HIV. In this study, peripheral blood mononuclear cells (PBMCs) from people without HIV were exposed to tenofovir disoproxil fumarate (TDF) or emtricitabine (FTC) overnight. Mitochondrial mass and function were measured by flow cytometry and an Agilent XFp analyzer. Monocyte-derived macrophages (MDMs) were differentiated in 20% autologous serum for 5 days in the presence or absence of TDF or FTC, and surface markers, lipid uptake, and efferocytosis were measured by flow cytometry. MDM gene expression was measured using transcriptome sequencing (RNA-seq). Plasma lipids were measured using mass spectrometry. PBMCs exposed to TDF or FTC had decreased maximal oxygen consumption rate (OCR) and reduced mitochondrial mass. Exposure to PrEP also increased reactive oxygen species (ROS) production from monocyte subsets. Compared to MDMs cultured in medium alone, cells differentiated in the presence of TDF (829 genes) or FTC (888 genes) had significant changes in gene expression. Further, PrEP-exposed MDMs had decreased mitochondrial mass and displayed increased lipid uptake and reduced efferocytosis. Plasma biomarkers and lipid levels were also altered in vivo in individuals receiving a PrEP regimen. In conclusion, exposure of leukocytes to TDF or FTC resulted in decreased mitochondrial function and altered functional and transcriptional profiles. These findings may have important implications for the metabolic and immunologic consequences of PrEP in populations at risk for HIV acquisition.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available