Treatment of HSV Breakout
For an active HSV breakout, initiate oral valacyclovir 1 gram twice daily for 7-10 days for first episodes, or 500 mg twice daily for 3-5 days for recurrent episodes, starting treatment within 24-72 hours of symptom onset for maximum effectiveness. 1, 2
First-Line Treatment Options
The choice of antiviral therapy depends on whether this is a first episode or recurrent outbreak:
First Clinical Episode (Initial Outbreak)
- Valacyclovir 1 g orally twice daily for 7-10 days (preferred due to convenient dosing) 1, 2, 3
- Acyclovir 400 mg orally three times daily for 7-10 days 1, 4, 5
- Acyclovir 200 mg orally five times daily for 7-10 days 1, 4
- Famciclovir 250 mg orally three times daily for 7-10 days 1, 2, 6
- Treatment may be extended beyond 10 days if healing is incomplete 1, 2
Recurrent Episodes
- Valacyclovir 500 mg orally twice daily for 3-5 days (most convenient and effective) 1, 2, 3
- Acyclovir 400 mg orally three times daily for 5 days 1, 4
- Acyclovir 800 mg orally twice daily for 5 days 2
- Famciclovir 125 mg orally twice daily for 5 days 1, 2, 6
Treatment is most effective when initiated during the prodromal period or within 24 hours of lesion onset—delaying beyond 72 hours significantly reduces effectiveness. 1, 4, 2, 5
Location-Specific Considerations
Genital HSV
All the standard regimens above apply, with valacyclovir offering the advantage of twice-daily dosing that improves adherence. 2, 3
Orolabial HSV (Cold Sores/Herpes Labialis)
- Famciclovir 1500 mg as a single dose (most convenient for cold sores) 4, 6
- Valacyclovir 2 grams twice daily for 1 day 4, 3
- Standard multi-day regimens listed above also effective 4, 5
Severe Mucocutaneous Disease
- Acyclovir 5-10 mg/kg IV every 8 hours for severe disease requiring hospitalization 1, 4
- Switch to oral therapy once lesions begin to regress 1
- Continue treatment until complete healing 1
Special Populations
HIV-Infected or Immunocompromised Patients
- Higher doses and longer duration required: Acyclovir 400 mg orally 3-5 times daily until clinical resolution 1, 4
- Famciclovir 500 mg twice daily effective for reducing recurrences and viral shedding 1, 4, 2
- Short-course therapy (1-3 days) should NOT be used in HIV-infected patients 1
- Monitor closely for treatment failure, which may indicate acyclovir resistance 1
Pregnant Women
Standard antiviral regimens can be used, though specific counseling about neonatal transmission risk is essential. 1
When to Consider Suppressive Therapy
If you experience 6 or more recurrences per year, daily suppressive therapy should be strongly considered: 1, 2
- Valacyclovir 500 mg-1 g orally once daily 1, 2
- Acyclovir 400 mg orally twice daily 1, 2
- Famciclovir 250 mg orally twice daily 1, 2
Suppressive therapy reduces recurrence frequency by ≥75% and also reduces asymptomatic viral shedding and transmission risk to partners. 1, 2 After 1 year of continuous suppressive therapy, reassess whether continuation is needed as recurrence frequency naturally decreases over time in many patients. 1
Critical Pitfalls to Avoid
Do NOT use topical acyclovir alone—it is substantially less effective than systemic oral therapy and is not recommended for HSV breakouts. 1, 2, 5, 7
Do NOT delay treatment—waiting beyond 72 hours of symptom onset significantly reduces antiviral effectiveness. 4, 2, 5
Do NOT use short-course therapy in immunocompromised patients—they require longer treatment durations. 1
Treatment Failure and Resistance
If lesions do not begin to resolve within 7-10 days of initiating therapy, suspect acyclovir resistance: 1, 2
- Obtain viral culture and susceptibility testing 1
- For confirmed acyclovir-resistant HSV, switch to IV foscarnet 40 mg/kg every 8 hours 1, 8
- Resistance is rare in immunocompetent patients but more common in immunocompromised individuals 1
Monitoring Requirements
No laboratory monitoring is needed for patients on oral antiviral therapy unless significant renal impairment exists. 1, 4, 2 For patients receiving high-dose IV acyclovir, monitor renal function at treatment initiation and once or twice weekly during treatment. 1, 2
Counseling and Transmission Prevention
Patients should abstain from sexual activity when lesions or prodromal symptoms are present. 1 Consistent condom use reduces HSV-2 transmission by approximately 50% and should be encouraged. 1, 2 Suppressive antiviral therapy (valacyclovir 500 mg daily) reduces transmission to uninfected partners by 50% in heterosexual couples. 1 However, asymptomatic viral shedding can still occur even on suppressive therapy, so transmission risk is reduced but not eliminated. 1