First-Line Antiviral Dosing for Initial HSV Outbreak
For a first episode of genital herpes, treat with valacyclovir 1 gram orally twice daily for 10 days, acyclovir 400 mg orally three times daily for 7-10 days, or famciclovir 250 mg orally three times daily for 7-10 days. 1
Treatment Regimens by HSV Location
Genital Herpes (First Clinical Episode)
The CDC provides three equally effective options for initial genital herpes treatment, all for 7-10 days duration: 1
- Valacyclovir 1 g orally twice daily (preferred for convenience) 1, 2
- Acyclovir 400 mg orally three times daily 1
- Acyclovir 200 mg orally five times daily 1
- Famciclovir 250 mg orally three times daily 1
Extend treatment beyond 10 days if healing remains incomplete. 1
Oral Herpes/Cold Sores (First Episode)
For herpes labialis, the CDC recommends the same dosing as recurrent episodes since most first presentations are actually recurrences: 3
- Valacyclovir 2 g orally twice daily for 1 day (12 hours apart, most convenient) 2
- Acyclovir 800 mg orally twice daily for 5 days 3
- Acyclovir 400 mg orally three times daily for 5 days 3
- Acyclovir 200 mg orally five times daily for 5 days 3
Critical Timing Considerations
Initiate therapy within 48 hours of symptom onset for maximum benefit. 1, 4 Treatment started during the prodrome (tingling, itching, burning) or within 2 days of lesion appearance provides optimal efficacy. 3, 4 Starting therapy after this window significantly reduces effectiveness. 4
Comparative Efficacy and Convenience
Valacyclovir achieves 3-5 times higher acyclovir blood levels than oral acyclovir due to superior bioavailability, allowing less frequent dosing while maintaining equivalent clinical efficacy. 5, 6 In a large randomized trial of 643 patients with first-episode genital herpes, valacyclovir 1000 mg twice daily was equally effective as acyclovir 200 mg five times daily for viral shedding duration, time to healing, and pain resolution. 6
Important Clinical Caveats
Avoid topical acyclovir—it is substantially less effective than oral formulations and is explicitly discouraged by the CDC. 4 Topical therapy provides no improvement in systemic symptoms and should not be used. 7
Counsel patients that antiviral therapy controls symptoms but does not eradicate latent virus. 1, 4 These medications do not affect subsequent recurrence risk, frequency, or severity after discontinuation. 3, 4
Patients must abstain from sexual activity when lesions or prodromal symptoms are present. 1 However, transmission can occur during asymptomatic periods due to viral shedding, so inform sex partners about the diagnosis and recommend condom use during all sexual exposures with new or uninfected partners. 1
Special Populations Requiring Modified Therapy
Immunocompromised patients require more aggressive treatment: 4
- Acyclovir 400 mg orally 3-5 times daily, or 4
- IV acyclovir 5-10 mg/kg every 8 hours for severe/disseminated disease 4
These patients experience more severe, prolonged episodes and higher risk of acyclovir resistance, particularly in HIV-infected individuals. 8, 7