In Vitro Exposure of Leukocytes to HIV Preexposure Prophylaxis Decreases Mitochondrial Function and Alters Gene Expression Profiles.
Emily R BowmanCheryl CameronBrian RichardsonManjusha KulkarniJanelle GabrielAaren KettelhutLane HornsbyJesse J KwiekAbigail Norris TurnerCarlos MalvestuttoJose BazanSusan L KoletarSusanne Doblecki-LewisMichael M LedermanMark CameronNichole R KlattJordan E LakeNicholas T FunderburgPublished in: Antimicrobial agents and chemotherapy (2020)
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.
Keyphrases
- men who have sex with men
- hiv positive
- hiv testing
- antiretroviral therapy
- gene expression
- hiv infected
- flow cytometry
- rna seq
- human immunodeficiency virus
- hiv aids
- single cell
- hiv infected patients
- reactive oxygen species
- genome wide
- dna methylation
- peripheral blood
- mass spectrometry
- hepatitis c virus
- fatty acid
- healthcare
- dendritic cells
- public health
- dna damage
- liquid chromatography
- stem cells
- mental health
- cell death
- bone marrow
- genome wide identification
- induced apoptosis
- south africa
- cell proliferation
- transcription factor
- social media
- heart rate
- endoplasmic reticulum stress
- resistance training
- climate change