Treatment of Herpes Simplex Virus (HSV)
For HSV infections, oral antiviral medications including valacyclovir, acyclovir, and famciclovir are the mainstay of treatment, with valacyclovir being preferred due to its convenient dosing and effectiveness in reducing symptoms and viral shedding. 1
First Clinical Episode Treatment
For first clinical episodes of genital herpes, longer treatment courses are recommended 1:
- Valacyclovir 1 g orally twice daily for 7-10 days
- Acyclovir 400 mg orally three times daily for 7-10 days
- Acyclovir 200 mg orally five times daily for 7-10 days
- Famciclovir 250 mg orally three times daily for 7-10 days
For orolabial lesions, treatment with oral valacyclovir, famciclovir, or acyclovir for 5-10 days is recommended 2
Severe mucocutaneous HSV lesions respond best to initial treatment with IV acyclovir 2
Recurrent Episodes Treatment
For recurrent genital herpes, shorter courses are recommended 3, 1:
- Valacyclovir 500 mg orally twice daily for 5 days (preferred option)
- Acyclovir 400 mg orally three times daily for 5 days
- Acyclovir 800 mg orally twice daily for 5 days
- Acyclovir 200 mg orally five times daily for 5 days
- Famciclovir 125 mg orally twice daily for 5 days
Episodic therapy is most effective when started during the prodrome or within 1 day after onset of lesions 3
Short-course therapy (1-3 days) should not be used in patients with HIV infection 2
Suppressive Therapy
Daily suppressive therapy is recommended for patients with frequent recurrences (≥6 episodes per year) 4, 3, 1:
- Valacyclovir 1 g orally once daily or 500 mg orally once daily
- Acyclovir 400 mg orally twice daily
- Famciclovir 250 mg orally twice daily
Suppressive therapy can reduce recurrence frequency by ≥75% and reduce asymptomatic viral shedding 3, 1
After 1 year of suppressive therapy, consider discontinuation to assess recurrence frequency 3
Special Populations
Immunocompromised Patients
For immunocompromised patients, higher doses of antivirals are recommended 4:
- Acyclovir 400 mg orally 3-5 times daily until clinical resolution
- Famciclovir 500 mg twice daily has been effective in reducing recurrences in HIV-infected patients 4
IV acyclovir is indicated for treatment of initial and recurrent mucosal and cutaneous HSV in immunocompromised patients 5
Severe Disease
- For severe HSV infections requiring hospitalization, acyclovir 5-10 mg/kg IV every 8 hours for 5-7 days or until clinical resolution is recommended 4, 5
Treatment Failure and Resistance
Treatment failure should be suspected if lesions do not begin to resolve within 7-10 days after initiation of therapy 2
For suspected acyclovir-resistant HSV, viral culture and susceptibility testing should be performed 2
The treatment of choice for acyclovir-resistant HSV is IV foscarnet 2, 6
Alternative options for resistant cases include topical trifluridine (TFT) for accessible lesions or intravenous cidofovir 6
Important Clinical Considerations
Topical acyclovir is substantially less effective than systemic treatment and is not recommended 4, 1
Treatment should be initiated as early as possible for optimal effectiveness, ideally within 72 hours of symptom onset 4, 1
No laboratory monitoring is needed for patients receiving antiviral therapy unless they have significant renal impairment 2, 4
Valacyclovir appears to be somewhat better than famciclovir for suppression of genital herpes and associated viral shedding 7
Prevention of Transmission
Suppressive therapy can reduce the risk of transmission to sexual partners 1
Patients should be counseled to abstain from sexual activity when lesions or prodromal symptoms are present 3, 1
Consistent condom use should be encouraged to reduce HSV-2 transmission 2, 1
HSV-2-seronegative HIV-infected persons should ask their partners to be tested using type-specific serology before initiating sexual activity 2