What is the first-line treatment for genital herpes?

First-Line Treatment for Genital Herpes

The first-line treatment for genital herpes is oral acyclovir 400 mg three times daily for 7-10 days for initial episodes, or valacyclovir 1 gram twice daily for 10 days as an equally effective alternative with a more convenient dosing schedule. 1, 2

Treatment Recommendations Based on Episode Type

Initial Episode

• Preferred regimens:
  • Acyclovir 400 mg orally three times daily for 7-10 days 1
  • Valacyclovir 1 gram orally twice daily for 10 days 2

Recurrent Episodes

• Preferred regimens:
  • Acyclovir 800 mg orally three times daily for 2 days
  • Valacyclovir 500 mg orally twice daily for 3 days 2
  • Valacyclovir 1 gram orally once daily for 5 days 2

Suppressive Therapy (for frequent recurrences ≥6 per year)

• Preferred regimens:
  • Acyclovir 400 mg orally twice daily
  • Valacyclovir 1 gram orally once daily 2
  • Valacyclovir 500 mg orally once daily (for patients with ≤9 recurrences per year) 2

Evidence-Based Considerations

Valacyclovir has demonstrated similar efficacy to acyclovir in clinical trials but offers the advantage of less frequent dosing, which may improve patient adherence 2, 3. The FDA-approved clinical trials showed that for initial episodes, both medications have comparable median time to lesion healing (9 days), cessation of pain (5 days), and cessation of viral shedding (3 days) 2.

For recurrent episodes, valacyclovir 500 mg twice daily for 5 days reduced median time to lesion healing to 4 days versus 6 days with placebo, and reduced viral shedding time to 2 days versus 4 days with placebo 2.

Special Populations

HIV-Infected Patients

• Higher oral doses are recommended: acyclovir 400 mg orally 3-5 times daily 1
• For suppressive therapy in HIV-infected patients: valacyclovir 500 mg twice daily 2

Pregnancy

• Acyclovir 200 mg five times daily for 5-10 days
• Valacyclovir 1 gram twice daily for 5-10 days 4
• After 36 weeks of pregnancy, prophylactic treatment with acyclovir 400 mg three times daily or valacyclovir 500 mg twice daily until delivery may be recommended to reduce the risk of Cesarean delivery due to active lesions 4

Renal Dose Adjustments

For patients with renal impairment, dose adjustments are necessary:

Acyclovir Dose Adjustments

Creatinine Clearance (mL/min)	Genital Herpes Recurrent	Genital Herpes Suppressive
≥50 (normal)	500 mg every 12 hours	1 gram every 24 hours
30-49	No reduction	No reduction
10-29	500 mg every 24 hours	500 mg every 24 hours
<10	500 mg every 24 hours	500 mg every 24 hours

Clinical Pearls and Pitfalls

• Early initiation is crucial: Treatment is most effective when started within 72 hours of symptom onset for initial episodes and within 24 hours for recurrent episodes 2, 5
• Suppressive therapy benefits: For patients with ≥6 recurrences per year, suppressive therapy can keep 55% of patients recurrence-free for 6 months and 34% recurrence-free for 12 months 2
• Transmission reduction: Valacyclovir suppressive therapy has been shown to reduce the risk of HSV-2 transmission in discordant couples 2
• Hydration importance: Ensure adequate hydration during treatment, especially with IV acyclovir, to prevent neurotoxicity 1

Symptomatic Relief

• Keep lesions clean and dry
• Topical anesthetics and sitz baths with warm water can provide pain relief
• Oral analgesics may be necessary for more severe pain 1

Patient Education

• Abstain from sexual activity during outbreaks or prodromal symptoms
• Use condoms consistently to reduce transmission risk
• Disclose HSV status to sexual partners
• Recognize that asymptomatic viral shedding can still lead to transmission 1