i agree [first-step phosphorylation in vivo] makes all the difference when it comes to potency - which can relate to resistance since you can shorten duration of viral exposure to drug - but i don't think it impacts on the inherent resistance barrier of the final active moiety.
I would argue that sub-therapeutic dosing of the active triphosphate metabolite (another way of saying that potency is inadequate) is a larger cause of drug resistance than any deficiencies in the inherent barriers of the motieties for the HCV nukes that have actually been tested.