HIV-infected T cells secrete simultaneously viral particles and small extracellular vesicles (sEVs) including MVB-derived exosomes and plasma membrane-derived EVs. sEVs and HIV share many physical and chemical characteristics, which makes their separation difficult.. Here, we used a global and un-biased proteomic approach to identify novel specific markers of the virus or sEV subtypes secreted by a human T lymphoma cell line.