What is the recommended duration for suppressive therapy with antiviral medications, such as valacyclovir (Valtrex) or acyclovir (Zovirax), for patients with recurrent cold sores?

Duration of Suppressive Therapy for Recurrent Cold Sores

For patients with frequent recurrent cold sores (≥6 episodes per year), suppressive therapy with valacyclovir 500 mg once daily should be continued for up to 1 year, after which discontinuation should be discussed to reassess recurrence frequency. 1, 2

Defining Candidates for Suppressive Therapy

• Suppressive therapy is indicated specifically for patients experiencing ≥6 episodes per year of recurrent cold sores 3
• This approach differs fundamentally from episodic treatment, which involves short-course therapy (1-3 days) initiated at the first sign of an outbreak 3
• Daily suppressive therapy reduces recurrence frequency by ≥75% in patients with frequent outbreaks 1, 2

Evidence-Based Duration Guidelines

Standard Duration (Immunocompetent Patients)

• The CDC establishes that safety and efficacy of valacyclovir for suppressive therapy has been documented for up to 1 year in immunocompetent patients 1, 2
• For comparison, acyclovir suppressive therapy has documented safety for up to 6 years of continuous use, though this longer duration data does not exist for valacyclovir 2

Reassessment After 1 Year

• After 1 year of continuous suppressive therapy, clinicians should discuss discontinuation with patients to assess current recurrence frequency 1, 2
• The rationale for this reassessment is that recurrence patterns may decrease over time, potentially eliminating the need for continued daily therapy 1
• This "drug holiday" allows both patient and provider to determine whether suppressive therapy remains necessary based on the patient's current disease burden 2

Dosing Regimens Based on Recurrence Frequency

Standard Recurrence Rate (<10 episodes/year)

• Valacyclovir 500 mg once daily is the recommended dose for patients with infrequent to moderate recurrences 1, 2

High Recurrence Rate (≥10 episodes/year)

• Valacyclovir 1000 mg once daily is recommended for patients with very frequent recurrences, as 500 mg once daily appears less effective in this population 1, 2

Special Populations Requiring Modified Duration

Immunocompromised Patients

• HIV-infected patients with CD4+ count ≥100 cells/mm³ require valacyclovir 500 mg twice daily (not once daily) 1, 2
• Safety data for suppressive therapy in HIV-infected patients extends only to 6 months of continuous use 2, 4
• Higher doses may be necessary due to more severe and frequent recurrences in this population 1

Athletes with Recurrent Herpes Gladiatorum

• Suppressive therapy should be strongly considered for athletes with recurrent herpes gladiatorum or herpes rugbiorum 1
• These patients should maintain adequate hydration to minimize nephrotoxicity risk 1

Critical Monitoring and Safety Considerations

• No laboratory monitoring is required for patients on suppressive therapy unless they have substantial renal impairment 1, 2
• For patients with creatinine clearance 30-49 mL/min, no dose reduction is needed 1
• Patients should be counseled to maintain adequate hydration throughout therapy 1, 4

Important Limitations and Patient Counseling Points

• Suppressive therapy reduces but does not eliminate asymptomatic viral shedding, meaning transmission risk persists even on therapy 1, 2
• Valacyclovir is not a cure for cold sores—it only suppresses recurrences 4
• No clinically significant acyclovir resistance has emerged in immunocompetent patients receiving suppressive therapy 2

Common Pitfalls to Avoid

• Do not confuse episodic treatment with suppressive therapy: Episodic treatment for cold sores involves high-dose, short-duration therapy (e.g., 2 g twice daily for 1 day), while suppressive therapy requires daily low-dose administration for months 3
• Do not prescribe valacyclovir 500 mg once daily for HIV-infected patients—they require 500 mg twice daily 2
• Do not continue suppressive therapy indefinitely without reassessment—the 1-year mark is the appropriate time to evaluate whether continued therapy is necessary 1, 2
• If lesions persist despite appropriate valacyclovir treatment, consider HSV resistance and viral culture with susceptibility testing 1, 2