Treatment of Herpes Simplex Virus (HSV) Infections
For first-episode genital herpes, treat with valacyclovir 1 g orally twice daily for 7-10 days, which is the preferred first-line therapy due to convenient dosing and superior effectiveness. 1
First Clinical Episode Treatment
The CDC recommends longer treatment courses for initial genital herpes episodes: 1, 2
- Valacyclovir 1 g orally twice daily for 7-10 days (preferred option) 1
- Acyclovir 400 mg orally three times daily for 7-10 days 1, 2
- Acyclovir 200 mg orally five times daily for 7-10 days 1, 2
- Famciclovir 250 mg orally three times daily for 7-10 days 1, 2
Extend treatment beyond 10 days if healing remains incomplete. 1, 2
For severe disease requiring hospitalization, the Infectious Diseases Society of America recommends IV acyclovir until lesions begin to regress, then transition to oral therapy. 2, 3
For first-episode herpes proctitis specifically, use acyclovir 400 mg orally five times daily for 10 days. 4
Recurrent Episodes Treatment
For recurrent outbreaks, the CDC recommends episodic therapy with valacyclovir 500 mg orally twice daily for 5 days as first-line treatment. 1, 5
Alternative regimens include: 1, 5
- 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
Critical timing consideration: Episodic therapy is most effective when started during the prodromal period or within 1 day after lesion onset. 1, 5 Treatment delayed beyond 72 hours significantly reduces effectiveness. 1
Common Pitfall
Most immunocompetent patients with recurrent disease do not benefit from acyclovir treatment when initiated late, which is why early patient-initiated therapy is essential. 4
Daily Suppressive Therapy
The CDC recommends daily suppressive therapy for patients with frequent recurrences (≥6 episodes per year): 1, 2, 5
- Valacyclovir 1 g orally once daily (for ≥10 episodes per year) 2
- Valacyclovir 500 mg orally once daily (for <10 episodes per year) 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 reduces asymptomatic viral shedding, which decreases transmission risk to sexual partners. 1, 2, 5
After 1 year of continuous suppressive therapy, discontinue treatment to reassess the patient's recurrence rate. 4, 1, 5
Special Populations
HIV-Infected Patients
HIV-infected patients require closer monitoring and may need longer treatment courses than HIV-negative patients. 1, 2
For suppressive therapy in HIV-infected patients, use: 2
- Valacyclovir 500 mg orally twice daily (higher dose than HIV-negative patients)
- Acyclovir 400 mg orally twice daily
Do not use short-course therapy (1-3 days) in HIV-infected patients. 2
Famciclovir 500 mg twice daily has demonstrated effectiveness in reducing recurrences and subclinical shedding in HIV-infected patients. 1
Pregnant Women
For pregnant women with genital herpes, acyclovir is the first-choice therapy based on decades of safety data. 2
Treatment approach: 2
- Episodic therapy for first-episode HSV disease and recurrences can be offered during pregnancy
- For women with a history of genital herpes, consider suppressive therapy starting at 36 weeks gestation to reduce HSV shedding at delivery and decrease the need for cesarean delivery
- Cesarean delivery is mandatory for women with visible genital lesions or prodromal symptoms at labor onset 2
Ciprofloxacin is contraindicated during pregnancy. 1
Treatment Failure and Acyclovir Resistance
If lesions do not begin to resolve within 7-10 days after initiating therapy, suspect treatment failure. 2
Causes of treatment failure include: 1
- Incorrect diagnosis
- Co-infection with another STD
- HIV infection
- Poor medication adherence
- Antiviral resistance
For confirmed acyclovir-resistant HSV, IV foscarnet is the treatment of choice. 1, 2, 6
Dosing for foscarnet: 6
- 40 mg/kg IV three times daily, or
- 60 mg/kg IV twice daily for 10 days or until complete lesion resolution
If foscarnet fails, consider IV cidofovir or topical cidofovir 1-3% ointment. 6
Resistance Risk Factors
Acyclovir resistance develops primarily in immunocompromised patients receiving long-term treatment and prophylaxis. 7 Resistance is rare in immunocompetent patients. 6, 8
Critical Clinical Considerations
Topical acyclovir is substantially less effective than oral therapy and should not be used. 4, 1, 5 This is a common prescribing error to avoid.
Systemic antiviral drugs partially control symptoms but do not eradicate latent virus or affect subsequent recurrences after discontinuation. 4, 1
Patients must be counseled to: 2, 5
- Abstain from sexual activity when lesions or prodromal symptoms are present
- Use condoms consistently during all sexual exposures with new or uninfected partners
- Understand that asymptomatic viral shedding can occur and may lead to transmission
The same medication dosages and frequencies are recommended for genital HSV-1 infection as for HSV-2. 1
Monitoring Requirements
No laboratory monitoring is needed in patients receiving episodic or suppressive therapy unless they have substantial renal impairment. 2 For patients receiving high-dose IV acyclovir, monitor renal function at treatment initiation and once or twice weekly during treatment. 2