I've got and Edirol FA101 and Motu 828 mk1 aggregate device, and occasionally the sound disappears when I add an instrument plugin (Uhe Diva) or similiar. It's hard to figure out what does it, but it might be a buffer overrun or clock sync issue?
Happens intermittently, and randomly. Usually I fix it by opening prefs and selecting the FA101 by itself and then reselecting the aggregate device again.
OSX 10.10.5/ Renoise 3.1