What is the recommended treatment for herpes simplex suppression therapy?

Herpes Simplex Suppression Therapy

For herpes simplex suppression therapy, the recommended regimens are acyclovir 400 mg orally twice daily, famciclovir 250 mg orally twice daily, or valacyclovir 500-1000 mg orally once daily, with medication choice based on patient-specific factors including frequency of recurrences. 1, 2

Indications for Suppressive Therapy

• Suppressive therapy is recommended for patients with frequent recurrences (six or more recurrences per year) 1, 2
• Daily suppressive therapy reduces the frequency of genital herpes recurrences by ≥75% among patients with frequent recurrences 1, 2
• Suppressive therapy has been documented as safe and effective for acyclovir for up to 6 years, and for valacyclovir and famciclovir for 1 year 1

Recommended Medication Regimens

Standard Regimens for Immunocompetent Patients:

• Acyclovir 400 mg orally twice daily 1
• Famciclovir 250 mg orally twice daily 1, 3
• Valacyclovir 250 mg orally twice daily 1
• Valacyclovir 500 mg orally once daily 1, 4
• Valacyclovir 1,000 mg orally once daily 1, 4

Special Considerations for HIV-Infected Patients:

• Valacyclovir suppressive therapy should be 500 mg twice daily rather than once daily 1, 2
• For HIV-infected patients with CD4+ cell count ≥100 cells/mm³, the recommended dosage is 500 mg twice daily 4

Medication Selection Algorithm

1. For patients with <10 recurrences per year:

   • Valacyclovir 500 mg once daily is effective and offers convenient dosing 5, 6
   • Alternative: Acyclovir 400 mg twice daily or famciclovir 250 mg twice daily 1

2. For patients with ≥10 recurrences per year:

   • Valacyclovir 1 gram once daily 5
   • Valacyclovir 250 mg twice daily 5
   • Acyclovir 400 mg twice daily 5, 7
   • Note: Valacyclovir 500 mg once daily appears less effective for very frequent recurrences 1, 2

3. For HIV-infected patients:

   • Valacyclovir 500 mg twice daily 1, 4
   • Alternative: Acyclovir 400 mg twice daily 1

Clinical Pearls and Pitfalls

• Suppressive therapy reduces but does not eliminate asymptomatic viral shedding, so the risk of transmission is reduced but not eliminated 1, 2
• After 1 year of continuous suppressive therapy, consider discontinuation to assess the patient's recurrence rate, as frequency often decreases over time 1
• No laboratory monitoring is needed in patients receiving suppressive therapy unless they have substantial renal impairment 1, 2
• Resistance to antiviral medications is rare in immunocompetent patients but should be suspected if lesions do not begin to resolve within 7-10 days of therapy 1, 2
• Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome has been reported with high-dose valacyclovir (8 g/day) but not at doses used for HSV suppression 1, 8

Efficacy Considerations

• All recommended regimens have demonstrated efficacy in clinical trials 5, 7, 6
• Once-daily valacyclovir regimens offer a more convenient dosing option with comparable efficacy to twice-daily acyclovir 9, 6
• In a large-scale dose-finding study, all valacyclovir dosages were significantly more effective than placebo at preventing recurrences (p<0.0001) 5
• After 16 weeks of treatment, 69% of patients receiving valacyclovir 500 mg daily remained recurrence-free compared with only 9.5% of patients on placebo 6

Duration of Therapy

• Safety and efficacy have been documented for acyclovir for up to 6 years 1
• For valacyclovir and famciclovir, safety and efficacy have been established for up to 1 year 1, 3
• The full preventive effect builds gradually, with significant reduction in outbreaks typically occurring within the first few weeks of consistent therapy 2