What is the treatment for genital Herpes Simplex Virus (HSV)?

Treatment for Genital Herpes Simplex Virus (HSV)

Oral antiviral therapy with valacyclovir, acyclovir, or famciclovir is the mainstay of treatment for genital HSV, with specific regimens depending on whether this is a first episode, recurrent episode, or requires suppressive therapy. 1, 2, 3

First Clinical Episode

For patients presenting with their first episode of genital herpes, longer treatment courses are required:

• Valacyclovir 1 gram orally twice daily for 7-10 days is the preferred regimen due to convenient dosing 2, 3, 4
• Alternative options include:
  • Acyclovir 400 mg orally three times daily for 7-10 days 1, 2
  • Acyclovir 200 mg orally five times daily for 7-10 days 5, 2
  • Famciclovir 250 mg orally three times daily for 7-10 days 2, 3
• Treatment may be extended beyond 10 days if healing is incomplete 2, 3

The rationale for longer treatment in first episodes is that primary infections typically have more extensive disease and prolonged viral shedding compared to recurrences. 5

Recurrent Episodes (Episodic Therapy)

For patients with recurrent outbreaks, shorter 5-day courses are effective:

• Valacyclovir 500 mg orally twice daily for 5 days is recommended as first-line therapy 5, 1, 2
• Alternative regimens include:
  • Acyclovir 400 mg orally three times daily for 5 days 5, 1
  • Acyclovir 800 mg orally twice daily for 5 days 5, 1
  • Acyclovir 200 mg orally five times daily for 5 days 5, 1
  • Famciclovir 125 mg orally twice daily for 5 days 5, 1

Critical timing consideration: Episodic therapy is most effective when started during the prodrome or within 1 day after onset of lesions. 5, 1, 2 Patients should be provided with medication or a prescription to self-initiate treatment at the first sign of symptoms. 2, 3 Treatment delayed beyond 72 hours significantly reduces effectiveness. 3

Daily Suppressive Therapy

For patients with frequent recurrences (≥6 episodes per year), daily suppressive therapy is indicated:

• Valacyclovir 1 gram orally once daily is the preferred regimen 1, 2
• Alternative suppressive regimens:
  • Valacyclovir 500 mg orally once daily 5, 1, 2
  • Acyclovir 400 mg orally twice daily 5, 1, 2
  • Famciclovir 250 mg orally twice daily 5, 1, 2

Important note: Valacyclovir 500 mg once daily appears less effective in patients with very frequent recurrences (≥10 episodes per year), so the 1 gram daily dose should be used in this population. 5

• Suppressive therapy reduces recurrence frequency by ≥75% 5, 1, 2
• Safety and efficacy documented for acyclovir up to 6 years and valacyclovir/famciclovir for 1 year 5, 1, 2
• After 1 year of continuous suppressive therapy, discontinue to reassess recurrence frequency, as recurrence rates often decrease over time 5, 1, 2

Suppressive therapy also reduces asymptomatic viral shedding and may reduce transmission risk to sexual partners, though it does not eliminate transmission risk entirely. 5, 1, 3

Severe Disease Requiring Hospitalization

For patients with severe disease or complications (disseminated infection, encephalitis, pneumonitis, hepatitis):

• Acyclovir 5-10 mg/kg IV every 8 hours for 5-7 days or until clinical resolution 5, 2
• Renal function should be monitored at treatment initiation and once or twice weekly during IV therapy 3

Special Populations

HIV-Infected Patients

• May require longer courses of therapy than HIV-negative patients 3
• Famciclovir 500 mg twice daily has been effective in reducing recurrences in this population 3
• Monitor closely for acyclovir resistance, which is more common in immunocompromised patients 2, 3

Pregnant Women

• Should inform healthcare providers about HSV infection 2, 3
• Routine suppressive therapy during pregnancy for recurrent genital herpes is not recommended by CDC, though safety of acyclovir and valacyclovir in pregnancy has not been definitively established 1

Treatment Resistance

Suspect acyclovir resistance if lesions do not begin to resolve within 7-10 days of therapy 1, 3:

• Obtain viral culture and susceptibility testing to confirm resistance 3
• For confirmed acyclovir-resistant HSV, use IV foscarnet 40 mg/kg every 8 hours 1, 3
• Resistance is rare in immunocompetent patients but more common in immunocompromised individuals 2, 3

Critical Clinical Pitfalls

Topical acyclovir is substantially less effective than oral therapy and should NOT be used 5, 1, 2, 3. This is a common mistake—topical formulations do not improve systemic symptoms and provide minimal benefit. 5

Avoid valacyclovir 8 grams per day in immunocompromised patients, as this high dose is associated with hemolytic uremic syndrome/thrombotic thrombocytopenic purpura. 1

Patient Counseling and Transmission Prevention

Patients must understand several key points:

• Abstain from sexual activity when lesions or prodromal symptoms are present 5, 2, 3
• Inform sex partners about having genital herpes 5, 2, 3
• Use condoms consistently during all sexual exposures, which reduces transmission risk by approximately 50% 5, 3
• Asymptomatic viral shedding can occur and lead to transmission, occurring more frequently with HSV-2 than HSV-1 and in patients with infection <12 months 5, 2
• Antiviral medications control symptoms but do not eradicate latent virus or prevent all recurrences 1, 2
• Childbearing-aged women should inform prenatal care providers about HSV infection due to neonatal transmission risk 5, 2

HSV-1 vs HSV-2 Considerations

• HSV-1 causes 5-30% of first-episode genital herpes cases 2
• Clinical recurrences are much less frequent with genital HSV-1 than HSV-2 2
• The same medication dosages and frequencies are recommended for genital HSV-1 as for HSV-2 3
• Identification of the infecting strain has prognostic importance and may be useful for counseling 2