Background: 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
(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 their effects on HIV infection.
EVs and EV-free plasma were purified from autologous blood
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
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.
–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.