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J Acquir Immune Defic Syndr. 2020 Jan 1;83(1):90-98. doi: 10.1097/QAI.0000000000002233.

Semen Extracellular Vesicles From HIV-1-Infected Individuals Inhibit HIV-1 Replication In Vitro, and Extracellular Vesicles Carry Antiretroviral Drugs In Vivo.

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Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA.
Medical Service, Iowa City Veterans Affairs Medical Center, Iowa City, IA.
Department of Pharmacology, Stony Brook University School of Medicine, Stony Brook, NY.
Antiviral Pharmacology Laboratory, College of Pharmacy, UNMC Center for Drug Discovery, University of Nebraska Medical Center, Omaha, NE.



Extracellular vesicles (EVs) are cell-derived vesicles with diverse functions in intercellular communication including disease and infection, and EVs seem to influence HIV-1 pathogenesis. EVs isolated from HIV-1-uninfected semen (SE), but not blood (BE), contain factors that interfere with HIV-1 infection and replication in target cells. The reason for this dichotomy is unknown. Furthermore, the effect of HIV-1 infection and antiretroviral (ARV) drugs on the anti-HIV-1 effects of SE and BE is unknown. Here, we characterize EVs and EV-free plasma isolated from HIV-infected donor semen and blood and their effects on HIV infection.


EVs and EV-free plasma were purified from autologous blood and semen of HIV-negative, HIV-infected antiretroviral therapy (ART)-naïve, and HIV-infected ART-treated participants. HIV infection was assessed in a TZM-bl cell reporter system. ARV concentrations were analyzed using liquid chromatography-mass spectrometry.


SE isolated from both HIV-negative and HIV-infected, ART-naïve donors inhibited HIV-1 infection, but BE and semen and blood EV-free plasma did not. By contrast, BE, SE, and EV-free plasma from HIV-infected, ART-treated donors inhibited HIV-1. Importantly, exosomes isolated from ART-treated donors contained concentrations of ARV drugs (ART-EVs) at biologically relevant inhibitory levels.


The HIV-1-inhibitory phenotype of SE is independent of donor HIV-1 or ART status, and ARV drugs and their metabolites are SE- and BE-associated in vivo.

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