What is the first line treatment for genital herpes?

First-Line Treatment for Genital Herpes

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, with treatment extended if healing is incomplete after 10 days. 1

Initial Episode Management

The treatment approach differs significantly between first episodes and recurrent disease:

First Clinical Episode

• Acyclovir 400 mg orally three times daily for 7-10 days is a primary recommended regimen 1
• Valacyclovir 1 g orally twice daily for 7-10 days offers equivalent efficacy with less frequent dosing 1
• Famciclovir 250 mg orally three times daily for 7-10 days is an equally effective alternative 1
• Alternative acyclovir dosing includes 200 mg orally five times daily for 7-10 days 2, 1
• Treatment duration should be extended beyond 10 days if lesions have not completely healed 1

Clinical trials demonstrate that valacyclovir 1 g twice daily and acyclovir 200 mg five times daily achieve identical outcomes for first episodes, with median time to lesion healing of 9 days, cessation of pain at 5 days, and cessation of viral shedding at 3 days. 3

Severe Disease Requiring Hospitalization

• Acyclovir 5-10 mg/kg IV every 8 hours for 5-7 days or until clinical resolution is indicated for severe presentations 2, 1
• Higher acyclovir dosages may be necessary for immunocompromised patients 1

Recurrent Episode Treatment

For established recurrent genital herpes, episodic therapy is the standard approach:

Episodic Therapy (Most Effective When Started During Prodrome or Within 24 Hours)

• Valacyclovir 500 mg orally twice daily for 5 days is the preferred CDC recommendation 4, 2
• Acyclovir 400 mg orally three times daily for 5 days 4, 2
• Acyclovir 800 mg orally twice daily for 5 days 4, 2
• Acyclovir 200 mg orally five times daily for 5 days 4, 2
• Famciclovir 125 mg orally twice daily for 5 days 4, 2

Valacyclovir 500 mg twice daily for 5 days reduces median time to lesion healing from 6 days (placebo) to 4 days, and cessation of viral shedding from 4 days to 2 days in patients with positive cultures. 3

Shortened Course Option

• Valacyclovir 500 mg twice daily for 3 days achieves comparable outcomes to the 5-day regimen, with median healing time of approximately 4.5 days in both groups 3
• This is the only FDA-approved 3-day episodic treatment regimen for recurrent genital herpes 5, 6

Suppressive Therapy for Frequent Recurrences

For patients experiencing ≥6 episodes per year, daily suppressive therapy is recommended:

Daily Suppressive Regimens

• Valacyclovir 1 g orally once daily (standard dose) 4, 2, 1
• Valacyclovir 500 mg orally once daily (alternative dose for patients with 9 or fewer recurrences per year) 4, 2, 1, 3
• Acyclovir 400 mg orally twice daily 4, 2, 1
• Famciclovir 250 mg orally twice daily 4, 2, 1

Suppressive therapy reduces recurrence frequency by ≥75% and significantly decreases asymptomatic viral shedding. 4, 1 In immunocompetent adults, 55% remained recurrence-free at 6 months and 34% at 12 months on valacyclovir 1 g daily, compared to only 7% and 4% on placebo. 3

Safety and Duration

• Acyclovir has documented safety for up to 6 years of continuous use 1
• Valacyclovir and famciclovir have documented safety for 1 year 1
• After 1 year of suppressive therapy, consider discontinuation to reassess recurrence frequency 4, 1

Critical Clinical Considerations and Pitfalls

What NOT to Use

• Topical acyclovir is substantially less effective than oral therapy and should not be used 4, 2, 1
• Valacyclovir 8 g per day is contraindicated due to risk of hemolytic uremic syndrome/thrombotic thrombocytopenic purpura in immunocompromised patients 4

Resistance Management

• Suspect acyclovir resistance if lesions fail to begin resolving within 7-10 days of therapy 4
• Foscarnet 40 mg/kg IV every 8 hours is the alternative for proven or suspected resistance 4
• Resistance is rare in immunocompetent patients but more common in immunocompromised individuals 2, 1

Special Populations

• HIV-infected patients: Valacyclovir 500 mg twice daily for 6 months achieved 65% recurrence-free rate versus 26% on placebo in patients on stable antiretroviral therapy 3
• Pregnancy: Routine suppressive therapy is not recommended during pregnancy for recurrent genital herpes, though acyclovir and valacyclovir safety data exist 4
• Pregnant women should inform healthcare providers about HSV infection for appropriate management decisions 1

Patient Education Essentials

• Initiate episodic therapy at first sign of prodrome or within 1 day of lesion onset for maximum effectiveness 4, 1
• Patients should have medication readily available to self-initiate treatment 1
• Abstain from sexual activity when lesions or prodromal symptoms are present 4, 2, 1
• Use condoms during all sexual exposures with new or uninfected partners 4, 2, 1
• Asymptomatic viral shedding can occur and lead to transmission 4, 2
• Antiviral medications control symptoms but do not eradicate the virus or prevent all recurrences 4, 1

HSV Type Considerations

• HSV-1 causes 5-30% of first-episode genital herpes cases but has much less frequent clinical recurrences than HSV-2 1
• Identifying the infecting strain (HSV-1 vs HSV-2) has prognostic importance for counseling 1
• Asymptomatic viral shedding occurs more frequently with HSV-2 infection and in patients with genital herpes for less than 12 months 1