What is the first-line treatment for herpes simplex virus (HSV)?

First-Line Treatment for Herpes Simplex Virus (HSV)

For first-episode genital herpes, the CDC recommends oral acyclovir 400 mg three times daily for 7-10 days, valacyclovir 1 g twice daily for 7-10 days, or famciclovir 250 mg three times daily for 7-10 days as equally effective first-line options. 1

Treatment by Clinical Presentation

First Clinical Episode of Genital Herpes

Recommended first-line regimens (all equally effective): 1

• Acyclovir 400 mg orally three times daily for 7-10 days 1
• Acyclovir 200 mg orally five times daily for 7-10 days 1
• Valacyclovir 1 g orally twice daily for 7-10 days 1, 2
• Famciclovir 250 mg orally three times daily for 7-10 days 1

Treatment is most effective when initiated within 48 hours of symptom onset, and may be extended beyond 10 days if healing is incomplete. 1, 2

Recurrent Genital Herpes Episodes

For episodic treatment of recurrences, the CDC recommends shorter courses: 3

• Valacyclovir 500 mg orally twice daily for 3-5 days 3, 2
• Acyclovir 400 mg orally three times daily for 5 days 3
• Acyclovir 800 mg orally twice daily for 5 days 3
• Famciclovir 125 mg orally twice daily for 5 days 3

Episodic therapy is most effective when started during prodrome or within 1 day of lesion onset. 3

Suppressive Therapy for Frequent Recurrences

For patients with ≥6 recurrences per year, daily suppressive therapy is recommended: 3

• Valacyclovir 1 g orally once daily (or 500 mg once daily for patients with ≤9 recurrences/year) 3, 2
• Acyclovir 400 mg orally twice daily 3
• Famciclovir 250 mg orally twice daily 3

Suppressive therapy reduces recurrence frequency by ≥75% and decreases asymptomatic viral shedding, though it does not eliminate transmission risk entirely. 3, 2

Orolabial Herpes (Cold Sores)

For herpes labialis, the CDC recommends: 4, 2

• Valacyclovir 2 g orally twice daily for 1 day (12 hours apart) 2

Treatment should be initiated at the earliest symptom (tingling, itching, or burning) for maximum effectiveness. 2

Key Clinical Considerations

Comparative Efficacy

• Valacyclovir and famciclovir offer improved bioavailability and more convenient dosing compared to acyclovir, though acyclovir remains effective and less expensive. 5, 6
• Valacyclovir demonstrates equivalent clinical efficacy to acyclovir in controlled trials. 4, 2
• One comparative study suggests valacyclovir may be somewhat more effective than famciclovir for suppression of viral shedding. 7

Critical Pitfalls to Avoid

• Never use topical acyclovir - it is substantially less effective than oral systemic therapy and its use is discouraged. 1, 3, 4
• Delaying treatment beyond 48-72 hours significantly reduces effectiveness. 8, 2
• For patients with very frequent recurrences (≥10 episodes/year), valacyclovir 500 mg once daily may be insufficient; use 1 g once daily instead. 4

Special Populations

• HIV-infected patients with CD4+ ≥100 cells/mm³: Valacyclovir 500 mg twice daily for suppressive therapy 2
• Immunocompromised patients: Require higher doses (acyclovir 400 mg orally 3-5 times daily) and longer treatment duration until clinical resolution 3, 8
• Severe disease requiring hospitalization: Acyclovir 5-10 mg/kg IV every 8 hours for 5-7 days or until clinical resolution 3, 8

Essential Patient Counseling

Patients must understand that: 1, 3, 4

• Genital herpes is incurable; antivirals control symptoms but do not eradicate latent virus 1, 4
• Abstain from sexual activity when lesions or prodromal symptoms are present 1, 4
• Asymptomatic viral shedding can occur, allowing transmission even without visible lesions 1, 3
• Condoms should be used during all sexual exposures with new or uninfected partners 1, 4