When herpes simplex virus (HSV) type 1 lesions are in the papule or vesicle stage, there is no benefit to starting oral acyclovir (strength of recommendation [SOR]: C, based on expert opinion). However, topical acyclovir 5% cream applied 5 times a day decreases pain and the duration of hard crust (SOR: B, extrapolated from randomized controlled trials [RCTs]). If started at the onset of symptoms (during the prodrome stage), acyclovir (400 mg 5 times daily for 5 days) decreases pain and healing time to loss of crust and valacyclovir (2 g twice daily for 1 day) reduces the lesion duration and time to healing and may prevent lesion development (SOR: A, based on RCTs)
