Poveda, EvaTabernilla, AndrésFitzgerald, WendySalgado-Barreira, ÁngelGrandal, MartaPérez, AlexandreMariño, AnaÁlvarez, HortensiaValcarce, NievesGonzález-García, JuanBernardino, José IgnacioGutierrez, FélixFujioka, HisashiCrespo, ManuelRuiz-Mateos, EzequielMargolis, LeonidLederman, Michael MFreeman, Michael L2023-05-032023-05-032022http://hdl.handle.net/10668/19805The role of extracellular vesicles (EVs) in human immunodeficiency virus (HIV) pathogenesis is unknown. We examine the cellular origin of plasma microvesicles (MVs), a type of ectocytosis-derived EV, the presence of mitochondria in MVs, and their relationship to circulating cell-free mitochondrial deoxyribonucleic acid (ccf-mtDNA) in HIV-infected patients and controls. Five participant groups were defined: 30 antiretroviral therapy (ART)-naive; 30 ART-treated with nondetectable viremia; 30 elite controllers; 30 viremic controllers; and 30 HIV-uninfected controls. Microvesicles were quantified and characterized from plasma samples by flow cytometry. MitoTrackerDeepRed identified MVs containing mitochondria and ccf-mtDNA was quantified by real-time polymerase chain reaction. Microvesicle numbers were expanded at least 10-fold in all HIV-infected groups compared with controls. More than 79% were platelet-derived MVs. Proportions of MVs containing mitochondria (22.3% vs 41.6%) and MV mitochondrial density (706 vs 1346) were significantly lower among HIV-infected subjects than controls, lowest levels for those on ART. Microvesicle numbers correlated with ccf-mtDNA levels that were higher among HIV-infected patients. A massive release of platelet-derived MVs occurs during HIV infection. Some MVs contain mitochondria, but their proportion and mitochondrial densities were lower in HIV infection than in controls. Platelet-derived MVs may be biomarkers of platelet activation, possibly reflecting pathogenesis even in absence of HIV replication.enAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/HIVelite controllersextracellular vesiclesmicrovesiclesmitochondriaCell-Derived MicroparticlesDNA, MitochondrialExtracellular VesiclesHIV InfectionsHumansTetraspanin 29Viremiaresearch article32603406open access10.1093/infdis/jiaa3751537-6613PMC8922002https://academic.oup.com/jid/advance-article-pdf/doi/10.1093/infdis/jiaa375/33537679/jiaa375.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8922002/pdf