Treatment of HSV-1 Infection
For HSV-1 infections, initiate oral antiviral therapy with acyclovir, valacyclovir, or famciclovir at the first sign of symptoms, with specific dosing regimens depending on whether this is a first episode, recurrent outbreak, or requires suppressive therapy. 1
First Clinical Episode
For initial HSV-1 infections, treatment duration is longer than recurrent episodes:
- Acyclovir 400 mg orally three times daily for 7-10 days 1
- Alternative: Acyclovir 200 mg orally five times daily for 7-10 days 1
- Alternative: Famciclovir 250 mg orally three times daily for 7-10 days 1
- Alternative: Valacyclovir 1 g orally twice daily for 7-10 days 1
Extend treatment beyond 10 days if healing is incomplete 1. For herpes proctitis or severe oral infection, higher dosing may be required (acyclovir 400 mg orally five times daily) 1.
Recurrent Episodes (Episodic Therapy)
Treatment must be initiated at the first sign of prodrome or within 1 day of lesion onset for maximum effectiveness 1. Standard regimens include:
- Acyclovir 400 mg orally three times daily for 5 days 2, 1
- Alternative: Acyclovir 800 mg orally twice daily for 5 days 2, 1
- Alternative: Acyclovir 800 mg orally three times daily for 2 days 1
- Alternative: Famciclovir 125 mg orally twice daily for 5 days 2
- Alternative: Valacyclovir 500 mg orally twice daily for 5 days 2
For herpes labialis (cold sores), single-day high-dose regimens have shown effectiveness:
- Famciclovir 1500 mg as a single dose 1
- Famciclovir 750 mg twice daily for 1 day 1
- Valacyclovir 2 g twice daily for 1 day 1
Suppressive Therapy
For patients with frequent recurrences (≥6 episodes per year), daily suppressive therapy reduces recurrence frequency by ≥75% 2, 1:
- Acyclovir 400 mg orally twice daily 2, 1
- Alternative: Valacyclovir 500 mg once daily 2, 1
- Alternative: Valacyclovir 1 g once daily (for patients with ≥10 recurrences per year) 1
- Alternative: Famciclovir 250 mg orally twice daily 2
Safety has been documented for acyclovir for up to 6 years and valacyclovir/famciclovir for 1 year 2, 1. After 1 year of continuous suppressive therapy, reassess the need for ongoing treatment 2.
Severe Disease Requiring Hospitalization
For severe HSV-1 disease with complications such as disseminated infection, pneumonitis, hepatitis, or CNS involvement (meningitis, encephalitis):
- Acyclovir 5-10 mg/kg IV every 8 hours for 5-7 days or until clinical resolution 2
Special Populations
Immunocompromised Patients (Including HIV-Infected)
Immunocompromised patients require longer courses of therapy and closer monitoring, as healing may be slower and treatment failures more common 2:
- Higher doses are often beneficial: Acyclovir 400 mg orally three to five times daily 2
- Continue therapy until clinical resolution is attained 2
- For severe cases: Acyclovir 5 mg/kg IV every 8 hours 2
If lesions persist despite acyclovir treatment, suspect resistance 2. For proven or suspected acyclovir-resistant strains:
- Foscarnet 40 mg/kg IV every 8 hours until clinical resolution 2
- Alternative: Topical cidofovir gel 1% applied once daily for 5 consecutive days 2
Note that all acyclovir-resistant strains are resistant to valacyclovir, and most are resistant to famciclovir 2.
Pregnancy
The safety of systemic acyclovir and valacyclovir in pregnancy has not been fully established, though current registry findings do not indicate increased risk for major birth defects 2.
Critical Clinical Considerations
Topical acyclovir is substantially less effective than oral therapy and should not be used 2, 1, 3.
Antiviral medications control symptoms but do not eradicate latent virus or affect the risk, frequency, or severity of recurrences after discontinuation 2, 1.
Suppressive therapy reduces but does not eliminate asymptomatic viral shedding 2, so transmission risk persists even on treatment.
Patient Counseling
Educate patients about: