Do you use valacyclovir as stepdown therapy for HSV CNS infections including encephalitis?

I have done this in selected patients who could not or did not wish to remain in the hospital for the full 14–21 days of IV acyclovir. For HSV meningitis, stepping down to oral valacyclovir after clinical improvement is an accepted approach. HSV encephalitis is different: IV acyclovir for 14–21 days remains the standard of care. There are limited pharmacokinetic data suggesting that high-dose oral valacyclovir can achieve potentially therapeutic acyclovir concentrations in the CSF, and it may be a reasonable alternative when IV acyclovir is simply not feasible, or there are major barriers to completing IV therapy.

But the evidence is thin, and we do not have good clinical data showing that oral therapy is equivalent to IV acyclovir for HSV e...

Yes. After initial improvement on IV acyclovir, I will typically transition to oral acyclovir at high doses to complete therapy.

Assuming no impairment of GI absorption and correct dosing, oral valacyclovir achieves therapeutic levels in the CNS.

Often but not always. I am increasingly using high-dose valacyclovir as “mop-up therapy,” although not routinely. While overall valacyclovir AUC levels may be similar to IV acyclovir, differences in peak concentrations, CNS penetration, and intracellular exposure remain uncertain, particularly as blood-brain barrier inflammation resolves. I would want to see a well-powered prospective trial demonstrating efficacy and safety before broadly adopting oral valacyclovir as step-down therapy for HSV CNS infections.