Treatment for Herpes Simplex Virus 2 (HSV-2)
For first clinical episodes of genital HSV-2, treat with valacyclovir 1 g orally twice daily for 7-10 days, and for recurrent episodes, use valacyclovir 500 mg orally twice daily for 5 days, starting treatment during the prodrome or within 1 day of lesion onset for maximum effectiveness. 1
First Clinical Episode Treatment
Treatment duration is longer for initial infections compared to recurrences because first episodes are typically more severe and prolonged. 1
Preferred regimen: Valacyclovir 1 g orally twice daily for 7-10 days 1
Alternative regimens include:
Extend treatment beyond 10 days if healing is incomplete 1
For severe first episodes requiring hospitalization (disseminated infection, encephalitis, pneumonitis, or hepatitis), use acyclovir 5-10 mg/kg IV every 8 hours for 5-7 days or until clinical resolution 2
Recurrent Episodes Treatment
Episodic therapy works best when initiated during prodromal symptoms or within 1 day after lesion onset; delayed treatment beyond 72 hours significantly reduces effectiveness. 1, 3
Preferred regimen: Valacyclovir 500 mg orally twice daily for 5 days 1, 3, 4
Alternative regimens include:
Clinical outcomes with valacyclovir 500 mg twice daily: Median time to lesion healing is 4 days, median time to cessation of viral shedding is 2 days, and median time to cessation of pain is 3 days 4
Daily Suppressive Therapy
Suppressive therapy is indicated for patients with frequent recurrences (≥6 episodes per year) and reduces recurrence frequency by ≥75%. 2, 1, 3
Alternative regimens include:
In immunocompetent adults, 55% remained recurrence-free at 6 months and 34% at 12 months with valacyclovir 1 g once daily 4
In HIV-infected adults, 65% remained recurrence-free at 6 months with valacyclovir 500 mg twice daily 4
Suppressive therapy reduces asymptomatic viral shedding and transmission risk to sexual partners 1, 5, 4
After 1 year of continuous suppressive therapy, discontinue medication to reassess the patient's recurrence rate 2, 1, 3
Safety has been documented for up to 5-6 years with acyclovir and valacyclovir 2, 3
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 HIV-infected patients 1
- Acyclovir resistance is more common in immunocompromised patients, particularly those with HIV 6, 7
Pregnant Women
- Routine suppressive therapy is not recommended during pregnancy for recurrent genital herpes, as the safety of systemic acyclovir and valacyclovir in pregnancy has not been definitively established 3
- Women of childbearing age with genital herpes should inform healthcare providers during pregnancy about their HSV infection due to neonatal infection risk 2
Critical Pitfalls and Considerations
Topical acyclovir is substantially less effective than oral therapy and should not be used. 2, 1, 3, 6, 8
- Antiviral medications control symptoms but do not eradicate latent virus or prevent all future recurrences after discontinuation 2, 1, 3, 8
- Most immunocompetent patients with recurrent disease do not benefit from acyclovir treatment if started late, which is why early initiation is critical 2
- Common side effects include nausea and headache; high-dose valacyclovir (8 g/day) is associated with hemolytic uremic syndrome/thrombotic thrombocytopenic purpura in immunocompromised patients and should be avoided 1, 3
- No laboratory monitoring is needed for patients on episodic or suppressive therapy unless substantial renal impairment exists 1
Treatment Failure and Resistance
Suspect acyclovir resistance if lesions do not begin to resolve within 7-10 days after initiating therapy. 1, 3, 7
- Obtain viral culture and perform susceptibility testing to confirm drug resistance 1
- For confirmed acyclovir-resistant HSV, use IV foscarnet 40 mg/kg every 8 hours as the treatment of choice 1, 3, 5, 7
- Acyclovir resistance remains low (<0.5%) in immunocompetent hosts but is more common in immunocompromised patients 5, 6
- If treatment failure occurs, also consider incorrect diagnosis, co-infection with another STD, HIV infection, or poor medication adherence 1
Transmission Prevention Counseling
Patients should abstain from sexual activity when lesions or prodromal symptoms are present. 2, 1, 3, 5
- Consistent condom use reduces HSV-2 transmission risk to sexual partners by approximately 50% 2, 1
- Asymptomatic viral shedding can occur even during suppressive therapy, potentially leading to transmission 2, 1, 3
- Suppressive therapy with valacyclovir 500 mg once daily reduced symptomatic HSV-2 acquisition by 75%, HSV-2 seroconversion by 50%, and overall HSV-2 acquisition by 48% in discordant couples 4
- Patients should inform sex partners about having genital herpes 3