What is the recommended treatment for patients with recurring herpes simplex virus (HSV) requesting maintenance doses after a recent breakout?

Treatment Guidelines for Recurrent Genital Herpes with Maintenance Therapy

For patients with recurrent genital herpes requesting maintenance therapy after a recent outbreak, initiate daily suppressive therapy with valacyclovir 1 gram orally once daily, or 500 mg once daily if the patient has 9 or fewer recurrences per year. 1, 2

Episodic Treatment for the Current Outbreak

Before starting maintenance therapy, treat the acute recurrent episode with one of the following CDC-recommended regimens:

• Valacyclovir 500 mg orally twice daily for 3-5 days (most convenient option) 1, 2
• Acyclovir 400 mg orally three times daily for 5 days 1
• Acyclovir 800 mg orally twice daily for 5 days 1
• Famciclovir 125 mg orally twice daily for 5 days 1

Episodic therapy is most effective when started during the prodrome or within 1 day after onset of lesions. 1 The 3-day valacyclovir regimen is FDA-approved and equally effective as the 5-day course for recurrent episodes. 2, 3

Indications for Daily Suppressive Therapy

Suppressive therapy should be strongly considered for patients with:

• ≥6 recurrences per year (reduces recurrence frequency by ≥75%) 1, 4
• Significant psychological distress from recurrent outbreaks 1
• Desire to reduce asymptomatic viral shedding and transmission risk 1

Suppressive Therapy Regimens

Standard Dosing (Immunocompetent Patients)

Primary recommendation:

• Valacyclovir 1 gram orally once daily 1, 2

Alternative regimens:

• Valacyclovir 500 mg orally once daily (for patients with ≤9 recurrences per year) 1, 2
• Acyclovir 400 mg orally twice daily 1
• Famciclovir 250 mg orally twice daily 1

Important caveat: Valacyclovir 500 mg once daily appears less effective than other dosing regimens in patients with very frequent recurrences (≥10 episodes per year), so use the 1 gram daily dose for these patients. 4

HIV-Infected Patients

• Valacyclovir 500 mg orally twice daily (not once daily) for patients with CD4+ count ≥100 cells/mm³ 2
• Higher doses may be needed for immunocompromised patients (acyclovir 400 mg orally 3-5 times daily until clinical resolution) 5, 6

Expected Outcomes and Timeline

• Suppressive therapy reduces recurrence frequency by ≥75% in patients with frequent recurrences 1, 4
• Most patients experience significant reduction in outbreaks within the first few weeks of consistent therapy 4
• Suppressive therapy reduces but does not eliminate asymptomatic viral shedding 4
• Safety and efficacy documented for acyclovir up to 6 years and valacyclovir/famciclovir for 1 year 4

Duration and Reassessment

• After 1 year of continuous suppressive therapy, consider discontinuation to reassess the patient's recurrence rate, as recurrence frequency often decreases over time 1, 4
• No laboratory monitoring is needed unless the patient has substantial renal impairment 4

Critical Patient Counseling Points

Patients must understand:

• Genital herpes is a recurrent, incurable viral disease—antiviral medications control symptoms but do not eradicate the virus 1
• Asymptomatic viral shedding can occur even on suppressive therapy, potentially leading to transmission 1, 4
• Abstain from sexual activity when lesions or prodromal symptoms are present 1
• Inform sex partners about having genital herpes 1
• Use condoms during all sexual exposures with new or uninfected partners 1

Common Pitfalls to Avoid

• Do not use topical acyclovir—it is substantially less effective than oral therapy and its use is discouraged 5, 1
• Do not delay episodic treatment beyond the prodrome or first day of lesions, as efficacy decreases significantly 1
• Do not use valacyclovir 500 mg once daily for patients with ≥10 recurrences per year—use 1 gram daily instead 4
• Do not prescribe valacyclovir 8 grams per day (associated with hemolytic uremic syndrome/thrombotic thrombocytopenic purpura in immunocompromised patients) 5
• Suspect acyclovir resistance if lesions do not begin to resolve within 7-10 days of therapy (rare in immunocompetent patients) 4

Special Considerations

Pregnancy: The safety of systemic acyclovir and valacyclovir in pregnancy has not been definitively established, though current registry findings do not indicate increased risk for major birth defects. 5 Routine suppressive therapy is not recommended during pregnancy for recurrent genital herpes. 5

Resistance: If lesions persist despite treatment, suspect HSV resistance to acyclovir. All acyclovir-resistant strains are resistant to valacyclovir, and most are resistant to famciclovir. Foscarnet 40 mg/kg IV every 8 hours is the alternative for proven or suspected resistance. 5