What is the recommended treatment for an adult or adolescent patient with a history of herpes simplex virus infection presenting with cold sores?

Cold Sore Treatment

For adults and adolescents with cold sores, initiate valacyclovir 2 grams twice daily for 1 day at the earliest sign of symptoms (prodrome), which reduces episode duration by approximately 1 day compared to placebo. 1, 2, 3

First-Line Treatment Options

Oral antiviral therapy is significantly more effective than topical formulations and should be the standard of care. 1 The CDC-recommended regimens for episodic treatment include:

Preferred Regimen

• Valacyclovir 2 grams twice daily for 1 day (most convenient, FDA-approved) 1, 2, 3
  • Reduces median episode duration by 1.0 day (p=0.001) 3
  • Reduces healing time and pain duration significantly 1, 3
  • Must be initiated during prodrome or within 2 hours of symptom onset for maximum benefit 1, 2

Alternative Regimens (if valacyclovir unavailable)

• Acyclovir 400 mg orally 3 times daily for 5 days 4, 1
• Acyclovir 800 mg orally 2 times daily for 5 days 1, 5
• Acyclovir 200 mg orally 5 times daily for 5 days 1
• Famciclovir 1500 mg as a single dose 1, 6

Critical Timing Considerations

Treatment must be initiated during the prodromal phase or within 24 hours of symptom onset. 1, 6 Peak viral titers occur in the first 24 hours after lesion onset, making early intervention essential for blocking viral replication. 6 Efficacy decreases significantly when treatment begins after lesions have fully developed (papule, vesicle, or ulcer stage). 2

Suppressive Therapy for Frequent Recurrences

For patients experiencing 6 or more recurrences per year, daily suppressive therapy reduces recurrence frequency by ≥75%. 6 Options include:

• Valacyclovir 500 mg once daily (can increase to 1000 mg for very frequent recurrences) 6
• Acyclovir 400 mg twice daily 6
• Famciclovir 250 mg twice daily 6

Safety and efficacy documented for acyclovir up to 6 years and valacyclovir/famciclovir for 1 year of continuous use. 6 After 1 year of suppressive therapy, consider discontinuation to reassess recurrence frequency, as it decreases over time in many patients. 6

Severe or Complicated Cases

For moderate to severe gingivostomatitis requiring hospitalization:

• Acyclovir 5-10 mg/kg IV every 8 hours until lesions begin to regress 4, 5, 6
• Then switch to oral acyclovir and continue until complete healing 4

For mild symptomatic gingivostomatitis:

• Acyclovir 20 mg/kg (maximum 400 mg/dose) orally 3 times daily for 5-10 days 4, 5

Acyclovir-Resistant HSV

For confirmed acyclovir-resistant infection (rare in immunocompetent patients at <0.5%, but up to 7% in immunocompromised):

• Foscarnet 40 mg/kg IV 3 times daily or 60 mg/kg IV twice daily 4, 5, 6, 7

Resistance should be suspected if lesions persist despite appropriate acyclovir therapy, particularly in immunocompromised patients. 6, 7 Obtain viral cultures and susceptibility testing when resistance is suspected. 7

Important Clinical Caveats

• Topical antivirals provide only modest benefit and are not effective for suppressive therapy as they cannot reach the site of viral reactivation 1, 6
• Acyclovir neither eradicates latent virus nor affects subsequent risk, frequency, or severity of recurrences after discontinuation 1
• Patients should abstain from activities that might spread the virus while lesions are present, though transmission can occur during asymptomatic periods 1
• Immunocompromised patients may require higher doses or longer treatment durations (acyclovir 400 mg orally 3-5 times daily) 5, 6
• Ensure adequate hydration as acyclovir is primarily renally excreted and requires dose adjustment in renal insufficiency 5

Patient Counseling on Triggers

Advise patients to identify and avoid personal triggers including ultraviolet light exposure, fever, psychological stress, and menstruation. 6 Consider prophylactic antiviral therapy before known trigger events (e.g., dental procedures, sun exposure). 6