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Massive release of CD9+ microvesicles in HIV infection, regardless of virologic control. BACKGROUND: The role of extracellular vesicles (EVs) in 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 DNA (ccf-mtDNA) in HIV-infected patients and controls. METHODS: Five participant groups were defined: 30 ART-naïve; 30 ART-treated with non-detectable viremia; 30 elite controllers; 30 viremic controllers; and 30 HIV-uninfected controls. MVs were quantified and characterized from plasma samples by flow cytometry. MitoTrackerDeepRed identified MVs containing mitochondria and ccf-mtDNA was quantified by real-time PCR. RESULTS: MV numbers were expanded at least 10-fold in all HIV-infected groups compared to 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. MV numbers correlated with ccf-mtDNA levels that were higher among HIV-infected patients. CONCLUSIONS: 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.