What is the recommended daily oral antiviral prophylaxis for an otherwise healthy adult with recurrent genital or oral herpes simplex virus infections?

Daily Oral Antiviral Prophylaxis for Recurrent Herpes Simplex Virus Infections

For otherwise healthy adults with recurrent genital or oral herpes, daily suppressive therapy with oral acyclovir 400 mg twice daily, valacyclovir 500 mg once daily (or 1000 mg once daily for ≥10 recurrences/year), or famciclovir 250 mg twice daily is highly effective and should be offered to patients with frequent or severe recurrences. 1, 2

When to Recommend Daily Suppressive Therapy

• Offer suppressive therapy to patients with ≥6 recurrences per year, as this population benefits most from daily prophylaxis with >75% reduction in recurrence frequency 1
• Consider suppressive therapy for patients with fewer recurrences if episodes are severe, psychologically distressing, or interfere with quality of life 1
• Suppressive therapy is appropriate for both genital and orolabial herpes simplex infections 1, 3

Recommended Dosing Regimens

First-Line Options (Choose One):

• Acyclovir 400 mg orally twice daily 1

  • Most extensively studied with documented safety for up to 6 years of continuous use 1
  • No clinically significant resistance has emerged in immunocompetent patients on long-term suppression 1

• Valacyclovir 500 mg orally once daily 1, 2, 4, 5

  • Preferred for patients with <10 recurrences per year due to convenient once-daily dosing 5
  • 69% of patients remained recurrence-free at 16 weeks compared to 9.5% on placebo 4
  • For patients with ≥10 recurrences per year, use valacyclovir 1000 mg once daily 1, 5

• Famciclovir 250 mg orally twice daily 1, 2

  • Comparable efficacy to acyclovir with twice-daily convenience 2
  • Safety and efficacy documented for 1 year of continuous use 1, 2

Specific Considerations for Orolabial Herpes:

• Valacyclovir 500 mg twice daily is effective for suppressing recurrent herpes labialis 3
• Sunscreen (SPF ≥15) alone can prevent UV-triggered recurrences and should be recommended alongside antiviral therapy 3
• Acyclovir 400 mg 2-3 times daily is an alternative for orolabial suppression 3

Duration and Reassessment

• After 1 year of continuous suppressive therapy, discontinue treatment temporarily to reassess recurrence frequency, as many patients experience decreased recurrence rates over time 1
• Restart suppressive therapy if recurrences return at a frequency that warrants prophylaxis 1
• Safety data support acyclovir use for up to 6 years; valacyclovir and famciclovir have 1-year safety data in guidelines, though longer use is common in practice 1

Important Caveats and Pitfalls

• Suppressive therapy reduces but does not eliminate asymptomatic viral shedding, so transmission risk persists even on daily antivirals 1
• Counsel patients to continue using latex condoms during all sexual activity to reduce HSV transmission risk 1
• Valacyclovir 500 mg once daily is less effective in patients with ≥10 recurrences per year—these patients require higher doses (1000 mg once daily) 1, 5
• Avoid the common error of prescribing episodic therapy doses (e.g., acyclovir 800 mg twice daily) for suppression—these higher doses are unnecessary and increase cost 1

What NOT to Do

• Do NOT use antiviral prophylaxis to prevent initial HSV infection after exposure—this is not recommended and has no proven efficacy 1, 6
• Do NOT prescribe suppressive therapy for patients who have infrequent, mild recurrences that do not impact quality of life 1
• Do NOT continue suppressive therapy indefinitely without periodic reassessment of need 1

Dose Adjustments for Renal Impairment

• For creatinine clearance 20-39 mL/min: Famciclovir 125 mg twice daily 2
• For creatinine clearance <20 mL/min: Famciclovir 125 mg once daily 2
• Similar renal dose adjustments apply to acyclovir and valacyclovir—consult prescribing information for specific adjustments 2

Special Populations

HIV-Infected Patients:

• For recurrent orolabial or genital herpes in HIV-infected adults, use higher doses: acyclovir 400 mg twice daily or famciclovir 500 mg twice daily for suppression 1
• These patients require more aggressive suppression due to more frequent and severe recurrences 1

Pregnancy:

• For pregnant women with frequent, severe recurrences, acyclovir prophylaxis may be indicated 1
• No pattern of adverse pregnancy outcomes has been reported with acyclovir exposure 1
• Oral acyclovir prophylaxis in late pregnancy to prevent neonatal transmission is controversial and not routinely recommended 1