What is the first-line treatment for genital herpes?

First-Line Treatment for Genital Herpes

For initial episodes of genital herpes, valacyclovir 1 gram orally twice daily for 7-10 days is the first-line treatment recommended by the CDC. 1, 2

Initial Episode Treatment

The CDC provides several effective antiviral regimens for first-episode genital herpes, all with comparable efficacy 2:

• 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, 2
• Acyclovir 200 mg orally five times daily for 7-10 days 2
• Famciclovir 250 mg orally three times daily for 7-10 days 2

Treatment should be extended beyond 10 days if healing remains incomplete. 1, 2 Clinical trial data demonstrate that valacyclovir 1 gram twice daily achieves median lesion healing in 9 days, with cessation of pain in 5 days and viral shedding in 3 days—outcomes equivalent to acyclovir 200 mg five times daily. 3

Recurrent Episode Treatment (Episodic Therapy)

For recurrent outbreaks, episodic therapy must be initiated during the prodrome or within 24 hours of lesion onset for maximum effectiveness 4, 2:

• Valacyclovir 500 mg orally twice daily for 5 days (most convenient) 1, 4, 2
• Acyclovir 400 mg orally three times daily for 5 days 1, 4, 2
• Acyclovir 800 mg orally twice daily for 5 days 4, 2
• Famciclovir 125 mg orally twice daily for 5 days 1, 4, 2

Patients should receive a prescription to self-initiate treatment at the first sign of prodromal symptoms or lesions. 1, 2 Valacyclovir reduces median time to lesion healing from 6 days (placebo) to 4 days, and viral shedding from 4 days to 2 days. 3

Suppressive Therapy for Frequent Recurrences

Daily suppressive therapy is recommended for patients experiencing ≥6 recurrences per year, reducing recurrence frequency by ≥75%. 1, 4, 2

Suppressive regimens include 4, 2:

• Valacyclovir 1 g orally once daily (only once-daily FDA-approved option) 4, 2, 3
• Valacyclovir 500 mg orally once daily (may be less effective with ≥10 episodes/year) 1, 4, 2
• Acyclovir 400 mg orally twice daily 4, 2
• Famciclovir 250 mg orally twice daily 4, 2

After 1 year of continuous suppressive therapy, consider discontinuation to reassess recurrence frequency. 4, 2 Safety data support acyclovir use for up to 6 years and valacyclovir/famciclovir for 1 year. 2

Critical Pitfalls to Avoid

• Never use topical acyclovir alone—it is substantially less effective than oral therapy. 1, 4, 2
• Do not delay episodic treatment beyond 72 hours of symptom onset, as efficacy diminishes significantly. 1
• Avoid valacyclovir 8 grams per day in immunocompromised patients due to risk of hemolytic uremic syndrome/thrombotic thrombocytopenic purpura. 4

Special Populations

For immunocompromised patients with severe disease requiring hospitalization, use acyclovir 5-10 mg/kg IV every 8 hours for 5-7 days. 2 If lesions fail to resolve within 7-10 days despite acyclovir therapy, suspect viral resistance and consider foscarnet 40 mg/kg IV every 8 hours. 4, 2

For HIV-infected patients with recurrent genital herpes, use famciclovir 500 mg twice daily for 7 days to account for increased viral replication. 2

Essential Patient Counseling

All patients must be counseled on 4, 2:

• The chronic, incurable nature of HSV infection with potential for recurrence 1, 4
• Abstaining from sexual activity when lesions or prodromal symptoms are present 4, 2
• Informing sexual partners about their HSV infection 4, 2
• Using condoms during all sexual exposures with new or uninfected partners 4, 2
• Asymptomatic viral shedding can occur and lead to transmission 4, 2
• Risk of neonatal infection, particularly for women of childbearing age 1, 2

HSV-1 causes 5-30% of first-episode genital herpes cases but has much less frequent clinical recurrences than HSV-2. 2 Identifying the infecting strain (HSV-1 vs HSV-2) has prognostic importance for counseling. 2