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, or valacyclovir 1 g twice daily for 7-10 days, or famciclovir 250 mg three times daily for 7-10 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
• Alternative first-episode regimens include:
  • Acyclovir 200 mg orally five times daily for 7-10 days 2, 1
  • Valacyclovir 1 g orally twice 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
• For severe herpes proctitis specifically, acyclovir 400 mg orally 5 times daily for 10 days is recommended 2

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 disease or complications 2, 1
• Higher dosages may be required for immunocompromised patients 1

Recurrent Episodes

For patients experiencing recurrent outbreaks, two treatment strategies exist:

Episodic Therapy (For Infrequent Recurrences)

• Valacyclovir 500 mg orally twice daily for 5 days is the preferred episodic regimen 3, 2
• Alternative episodic options include:
  • Acyclovir 400 mg orally three times daily for 5 days 3, 2
  • Acyclovir 800 mg orally twice daily for 5 days 3, 2
  • Acyclovir 200 mg orally five times daily for 5 days 3, 2
  • Famciclovir 125 mg orally twice daily for 5 days 3, 2
• Episodic therapy is most effective when started during prodrome or within 1 day of lesion onset 3, 1
• Patients should be provided medication or prescription to self-initiate at first symptoms 1

Suppressive Therapy (For Frequent Recurrences)

• Daily suppressive therapy is recommended for patients with ≥6 episodes per year 3, 2, 1
• Valacyclovir 1 g orally once daily is the preferred suppressive regimen and the only FDA-approved once-daily option 1, 4
• Alternative suppressive regimens include:
  • Valacyclovir 500 mg orally once daily 3, 2, 1
  • Acyclovir 400 mg orally twice daily 3, 2, 1
  • Famciclovir 250 mg orally twice daily 3, 2, 1
• Suppressive therapy reduces recurrence frequency by ≥75% 3, 1
• Safety has been documented for acyclovir up to 6 years and valacyclovir/famciclovir for 1 year 1
• After 1 year of continuous suppressive therapy, consider discontinuation to reassess recurrence frequency 3, 1

Clinical Efficacy Evidence

The FDA label data demonstrates that valacyclovir and acyclovir have comparable efficacy:

• In first-episode trials, both valacyclovir 1 g twice daily and acyclovir 200 mg 5 times daily showed median time to lesion healing of 9 days 5
• For recurrent episodes, valacyclovir 500 mg twice daily reduced median healing time to 4 days versus 6 days with placebo 5
• In suppressive therapy trials, valacyclovir 1 g once daily resulted in 55% of patients remaining recurrence-free at 6 months, comparable to acyclovir 400 mg twice daily 5

Critical Pitfalls to Avoid

• Never use topical acyclovir—it is substantially less effective than oral therapy 3, 2, 1
• Avoid valacyclovir 8 g 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; foscarnet 40 mg/kg IV every 8 hours is the alternative for proven or suspected resistance 3
• Antiviral resistance is rare in immunocompetent patients but more common in immunocompromised individuals 2, 1

Essential Patient Counseling

• Patients must abstain from sexual activity when lesions or prodromal symptoms are present 3, 2, 1
• Inform sex partners about having genital herpes 3, 1
• Use condoms during all sexual exposures with new or uninfected partners 3, 2, 1
• Asymptomatic viral shedding can occur and lead to transmission even without visible lesions 3, 2, 1
• Antiviral medications control symptoms but do not eradicate the virus or prevent all recurrences 3, 1
• HSV-2 causes more frequent recurrences than HSV-1, and asymptomatic shedding occurs more frequently with HSV-2 and in the first 12 months after infection 1

Special Populations

• Routine suppressive therapy is not recommended during pregnancy for recurrent genital herpes, though the safety of acyclovir and valacyclovir has not been definitively established 3
• Pregnant women with genital herpes should inform their healthcare providers about the HSV infection 1
• For HIV-infected patients on stable antiretroviral therapy, valacyclovir 500 mg twice daily for suppression resulted in 65% remaining recurrence-free at 6 months 5