What is the first line treatment for genital herpes?

First-Line Treatment for Genital Herpes

For first-episode genital herpes, the first-line treatment is valacyclovir 1 g orally twice daily for 7-10 days, with acyclovir 400 mg orally three times daily for 7-10 days as an equally effective alternative. 1, 2

Initial Episode Management

The CDC recommends several antiviral regimens for first clinical episodes, all with comparable efficacy 1:

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

Treatment duration may be extended beyond 10 days if healing is incomplete. 1, 2 Higher acyclovir dosages may be required in immunocompromised patients or severe cases. 1

Severe Disease Requiring Hospitalization

For severe disease or complications necessitating hospitalization, the CDC recommends acyclovir 5-10 mg/kg IV every 8 hours for 5-7 days or until clinical resolution. 1

Recurrent Episode Treatment

For recurrent genital herpes, valacyclovir 500 mg orally twice daily for 5 days is the first-line episodic therapy. 3, 1 Alternative regimens include 3, 1:

• 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 initiated during the prodrome or within 1 day after lesion onset. 3, 1 Patients should receive a prescription to self-initiate treatment at the first sign of symptoms. 1, 2

Suppressive Therapy for Frequent Recurrences

For patients with ≥6 recurrences per year, daily suppressive therapy with valacyclovir 1 g orally once daily is recommended. 3, 1, 2 This is the only antiviral approved for once-daily suppressive dosing. 4

Alternative suppressive regimens include 3, 1:

• Valacyclovir 500 mg orally once daily
• Acyclovir 400 mg orally twice daily
• Famciclovir 250 mg orally twice daily

Suppressive therapy reduces recurrence frequency by ≥75% and decreases asymptomatic viral shedding. 3, 1, 2 Safety has been documented for acyclovir up to 6 years and for valacyclovir up to 1 year. 3, 1 After 1 year of continuous suppressive therapy, consider discontinuation to reassess recurrence frequency. 3, 1

Critical Pitfalls to Avoid

• Never use topical acyclovir—it is substantially less effective than oral therapy and is not recommended. 3, 1, 2
• Avoid valacyclovir 8 grams per day in immunocompromised patients due to risk of hemolytic uremic syndrome/thrombotic thrombocytopenic purpura. 3
• Suspect acyclovir resistance if lesions do not begin resolving within 7-10 days of therapy; use foscarnet 40 mg/kg IV every 8 hours for proven or suspected resistance. 3
• Delaying treatment beyond 24 hours for recurrences significantly reduces efficacy. 2

Essential Patient Counseling

Patients must understand 3, 1:

• Genital herpes is a chronic, incurable viral disease with potential for recurrent episodes
• Antiviral medications control symptoms but do not eradicate the virus or prevent all recurrences
• Abstain from sexual activity when lesions or prodromal symptoms are present
• Inform all sex partners about having genital herpes
• Use condoms during all sexual exposures with new or uninfected partners
• Asymptomatic viral shedding can occur, potentially leading to transmission even without visible lesions
• HSV-2 causes more frequent asymptomatic shedding than HSV-1, particularly in the first 12 months after infection 1

Special Populations

Pregnant women with genital herpes must inform their healthcare providers about HSV infection. 1 Routine suppressive therapy is not recommended during pregnancy for recurrent genital herpes, though the safety of systemic acyclovir and valacyclovir has not been definitively established. 3 The risk of neonatal infection should be discussed with all patients, including men. 1, 2