Treatment for HSV-2 Outbreak
For a recurrent HSV-2 outbreak, start valacyclovir 500 mg orally twice daily for 5 days, initiated at the first sign of prodrome or within 1 day of lesion onset for maximum effectiveness. 1
First Episode vs. Recurrent Episode Treatment
The treatment approach differs significantly based on whether this is a first clinical episode or a recurrence:
First Clinical Episode
If this is the patient's first HSV-2 outbreak, longer treatment courses are required 1:
- Valacyclovir 1 g orally twice daily for 7-10 days (preferred due to convenient dosing) 2, 1
- Acyclovir 400 mg orally three times daily for 7-10 days 2, 1
- Acyclovir 200 mg orally five times daily for 7-10 days 2, 1
- Famciclovir 250 mg orally three times daily for 7-10 days 2, 1
Treatment may be extended beyond 10 days if healing is incomplete 2, 1
Recurrent Episodes
For established recurrent outbreaks, shorter 5-day courses are appropriate 1, 3:
- Valacyclovir 500 mg orally twice daily for 5 days (first-line choice) 1, 3
- Acyclovir 400 mg orally three times daily for 5 days 1, 3
- Acyclovir 800 mg orally twice daily for 5 days 1, 3
- Acyclovir 200 mg orally five times daily for 5 days 1, 3
- Famciclovir 125 mg orally twice daily for 5 days 1, 3
Timing Is Critical
Treatment must be initiated during the prodrome or within 1 day of lesion onset for optimal benefit. 1, 3 Delayed treatment beyond 72 hours significantly reduces effectiveness 1, 4. The median time to lesion healing with valacyclovir 500 mg is 4 days versus 6 days with placebo, and pain cessation occurs at 3 days versus 4 days 5.
When to Consider Suppressive Therapy
If the patient experiences ≥6 recurrences per year, daily suppressive therapy should be strongly considered 1, 3:
- Valacyclovir 1 g orally once daily (or 500 mg once daily for those with 9 or fewer recurrences) 1, 3
- Acyclovir 400 mg orally twice daily 1, 3
- Famciclovir 250 mg orally twice daily 1, 3
Suppressive therapy reduces recurrence frequency by ≥75% and decreases asymptomatic viral shedding 1, 3, 5. Safety has been documented for up to 6 years with acyclovir and 1 year with valacyclovir 2, 1. After 1 year of continuous suppressive therapy, reassess the patient to determine if continuation is needed 2, 1, 3.
Important Clinical Pitfalls to Avoid
Never use topical acyclovir—it is substantially less effective than oral therapy and is not recommended. 1, 4, 3 Systemic antiviral drugs partially control symptoms but do not eradicate latent virus or affect subsequent recurrences after discontinuation 1.
If lesions do not begin to resolve within 7-10 days of therapy, suspect acyclovir resistance and consider IV foscarnet 40 mg/kg every 8 hours 3, 6. Other reasons for treatment failure include incorrect diagnosis, co-infection with another STD, HIV infection, or poor medication adherence 1.
Special Populations
HIV-Infected Patients
HIV-infected patients may require longer treatment courses and closer monitoring 1. Famciclovir 500 mg twice daily has been effective in reducing recurrences and subclinical shedding in this population 1, 4.
Pregnant Women
Routine suppressive therapy is not recommended during pregnancy for recurrent genital herpes, though the safety of systemic acyclovir and valacyclovir has not been definitively established 3. Ciprofloxacin is contraindicated during pregnancy 1.
Transmission Prevention Counseling
Patients must be counseled to abstain from sexual activity when lesions or prodromal symptoms are present 2, 1, 3. Consistent condom use should be encouraged with all sexual partners 1. Suppressive therapy with valacyclovir 500 mg once daily reduces the risk of transmission to uninfected partners—in one study, symptomatic HSV-2 acquisition occurred in 0.5% of partners receiving valacyclovir versus 2.2% with placebo 5, 7. However, asymptomatic viral shedding can still occur even on suppressive therapy, and transmission remains possible 2, 1, 3.