Indication	First Choice	Alternative	Comments/Special Issues
Primary Prophylaxis	None.	None.	Primary prophylaxis is not indicated.
Secondary Prophylaxis	Mucocutaneous Disease: Acyclovir 20 mg/kg body weight/dose (maximum 800 mg/dose) by mouth BID Suppressive Therapy After Neonatal Skin, Eye, Mouth, or CNS Disease: Acyclovir 300 mg/m2 body surface area/dose by mouth TID for 6 months	Mucocutaneous Disease, For Adolescents Old Enough to Receive Adult Dosing: Valacyclovir 500 mg by mouth BID, or Famciclovir 500 mg by mouth BID	Secondary Prophylaxis Indicated: Suppressive secondary prophylaxis can be considered for children with severe and recurrent mucocutaneous (oral or genital) disease Criteria for Discontinuing Secondary Prophylaxis: After a prolonged period (e.g., 1 year) of prophylaxis, consider suspending prophylaxis and determine with the patient whether additional prophylaxis is necessary. Although level of immune reconstitution is a consideration, no specific CD4 threshold has been established.
Treatment	Neonatal CNS or Disseminated Disease: Acyclovir 20 mg/kg body weight IV/dose TID for ≥21 days Neonatal Skin, Eye, or Mouth Disease: Acyclovir 20 mg/kg body weight IV/dose TID for 14 days CNS or Disseminated Disease in Children Outside the Neonatal Period Acyclovir 10 mg/kg body weight (up to 20 mg/kg body weight/dose in children <12 years) IV TID for 21 days Moderate to Severe Symptomatic Gingivostomatitis: Acyclovir 5–10 mg/kg body weight/dose IV TID. Patients can be switched to oral therapy after lesions have begun to regress and therapy continued until lesions have completely healed. Mild Symptomatic Gingivostomatitis: Acyclovir 20 mg/kg body weight (maximum 400 mg/dose) dose by mouth QID for 7–10 days Recurrent Herpes Labialis: Acyclovir 20 mg/kg body weight (maximum 400 mg/dose) dose by mouth QID for 5 days For First-Episode Genital Herpes (Adults and Adolescents): Acyclovir 20 mg/kg body weight (maximim 400 mg/dose) dose by mouth TID for 7–10 days Recurrent Genital Herpes (Adults and Adolescents): Acyclovir 20 mg/kg body weight (maximum 400 mg/dose) dose by mouth TID for 5 days Children with HSV Keratoconjunctivitis: Often treated with topical trifluridine (1%) or acyclovir (3%) applied as 1–2 drops 5 times daily. Many experts add oral acyclovir to the topical therapy. Children with ARN: For children old enough to receive adult dose, acyclovir 10–15 mg/kg body weight/dose IV every 8 hours for 10–14 days, followed by oral valacyclovir 1 g/dose TID for 4–6 weeks As an alternative, oral acyclovir 20 mg/kg body weight/dose QID for 4–6 weeks after IV acyclovir for 10–14 days	Valacyclovir is approved for immunocompetent adults and adolescents with first-episode mucocutaneous HSV at a dose of 1 g/dose by mouth BID for 7–10 days; also approved for recurrent herpes labialis in children ≥12 years using two, 2 g doses by mouth separated by 12 hours as single-day therapy. Recurrent genital HSV can be treated with valacyclovir 500 mg BID for 3 days or 1 g by mouth daily for 5 days. Immunocompetent adults with recurrent herpes labialis can be treated with famciclovir, 1 g/dose by mouth BID for 1 day. Famciclovir is approved to treat primary genital HSV in immunocompetent adults at a dose of 250 mg/dose by mouth TID for 7–10 days. Recurrent genital HSV is treated with famciclovir 1 g/dose by mouth BID at a 12-hour interval for 2 doses Famciclovir is approved for use in HIV- infected adults and adolescents with recurrent mucocutaneous HSV infection at a dose of 500 mg/dose by mouth BID for 7 days. Acyclovir-Resistant HSV Infection: Foscarnet 40 mg/kg body weight/dose given IV TID (or 60 mg/kg body weight/dose BID) should be administered slowly over the course of 2 hours (i.e., no faster than 1 mg/kg/minute).	For Neonatal CNS Disease: Repeat CSF HSV DNA PCR should be performed on days 19 to 21 of therapy; do not stop acyclovir until repeat CSF HSV DNA PCR is negative. There is no pediatric preparation of valacyclovir (although crushed capsules can be used to make a suspension) and data on dosing in children are limited; can be used by adolescents able to receive adult dosing. There is no pediatric preparation of famciclovir and data on dosing in children are unavailable; can be used by adolescents able to receive adult dosing. Alternative and Short-Course Therapy in Immunocompromised Adults with Recurrent Genital Herpes: Acyclovir 800 mg per dose by mouth BID for 5 days Acyclovir 800 mg per dose by mouth TID for 2 days Note: Consultation with an ophthalmologist experienced in managing herpes simplex infection involving the eye and its complications in children is strongly recommended when ocular disease is present.

Key to Acronyms: ARN = acute retinal necrosis; BID = twice daily; CD4 = CD4 T lymphocyte; CNS = central nervous system; CSF = cerebrospinal fluid; HSV = herpes simplex virus; IV = intravenous; PCR = polymerase chain reaction; QID = four times daily; TID = three times daily