What are the recommended treatment options and dosing for oral herpes simplex (HSV‑1) in primary and recurrent episodes, including recommendations for healthy adults, immunocompromised patients, and pregnant women?

Treatment of Oral Herpes Simplex

Primary Episode Treatment

For first-episode oral HSV-1 infection, initiate valacyclovir 1 g orally twice daily for 7-10 days, extending treatment if healing is incomplete at day 10. 1

• Acyclovir 400 mg orally three times daily for 7-10 days is an effective alternative if valacyclovir is unavailable 1
• Treatment should begin as soon as the diagnosis is made, ideally within 72 hours of symptom onset 1
• Primary infections in otherwise healthy children generally do not require antiviral treatment, though severe cases—particularly in immunocompromised patients—may warrant intravenous acyclovir 2

Recurrent Episode Treatment (Cold Sores)

For recurrent oral herpes, start acyclovir 800 mg orally twice daily for 5 days during the prodrome or within 2 days of lesion onset. 3

Alternative Episodic Regimens (All for 5 Days)

The CDC provides three equally effective options for recurrent episodes 3:

• Acyclovir 800 mg orally twice daily (most convenient dosing) 3
• Acyclovir 400 mg orally three times daily 3, 1
• Acyclovir 200 mg orally five times daily 3
• Valacyclovir 500 mg orally twice daily 1
• Famciclovir 125 mg orally twice daily 1

Ultra-Short Course Options

For maximum convenience with comparable efficacy 3:

• Valacyclovir 2 g twice daily for 1 day 3
• Famciclovir 1500 mg single dose (reduces healing time from 6.2 to 4.4 days, p<0.001) 3

Critical Timing Considerations

• Treatment must be initiated during the prodrome or within 24 hours of lesion onset for maximum benefit 3, 1
• Starting therapy after 72 hours significantly reduces effectiveness 1
• Most immunocompetent patients with recurrent disease experience limited benefit from delayed therapy 3

Suppressive Therapy for Frequent Recurrences

For patients with ≥6 recurrences per year, prescribe daily suppressive therapy with acyclovir 400 mg orally twice daily, which reduces recurrence frequency by ≥75%. 1

Alternative Suppressive Regimens

• Valacyclovir 500 mg orally once daily (may be less effective with ≥10 episodes/year) 1
• Valacyclovir 250 mg orally twice daily 1
• Continue suppressive therapy for one year, then discontinue to reassess recurrence frequency, as episodes often decrease over time 1

Important Suppressive Therapy Caveats

• Suppressive therapy significantly lowers but does not eliminate asymptomatic viral shedding and transmission risk 1
• Acyclovir has a documented safety record of up to six years of continuous use 1

Topical Therapy: Limited Role

Oral antiviral medications are significantly more effective than topical formulations and should be prioritized. 3

• Topical acyclovir 5% cream may reduce lesion duration if applied very early, but is substantially less effective than systemic therapy 3, 1, 4
• Topical therapy alone is not recommended as primary treatment 1
• Penciclovir 1% cream and docosanol are alternatives, though comparative efficacy data are limited 5, 4

Special Populations

Immunocompromised Patients

Immunocompromised patients require oral or intravenous antiviral therapy due to risk of severe and prolonged episodes; topical treatment is inadequate. 3

• For severe HSV-1 disease, use acyclovir 400 mg orally 3-5 times daily until clinical resolution 5
• Intravenous acyclovir is indicated for disseminated infection or inability to tolerate oral therapy 2
• Prophylactic oral acyclovir may reduce frequency and severity of recurrent attacks, though optimal timing and duration vary 5

Pregnant Women

• Valacyclovir and acyclovir are generally considered safe during pregnancy for treatment of HSV infections 1
• Risk-benefit assessment should guide treatment decisions in consultation with obstetric care 1

Patient Counseling Essentials

Patients must understand that antiviral therapy neither eradicates latent virus nor affects subsequent risk, frequency, or severity of recurrences after discontinuation. 3

• Abstain from activities that might spread the virus while lesions are present 3
• Transmission can occur during asymptomatic periods, though less frequently with HSV-1 than HSV-2 1
• Sunscreen (SPF ≥15) alone can effectively prevent UV-triggered recurrences 4
• Provide a prescription for self-initiated treatment at first sign of recurrence 1

Common Pitfalls to Avoid

• Never delay treatment beyond 72 hours for recurrences 1
• Do not rely on topical acyclovir alone as primary therapy 1
• Do not use herpes zoster dosing regimens (800 mg five times daily) for oral HSV-1 3
• Recognize that most immunocompetent patients with infrequent recurrences may not require treatment, as episodes are self-limited 3