What is the first-line treatment for herpes simplex virus (HSV) infections?

First-Line Treatment for Herpes Simplex Virus (HSV) Infections

The first-line treatment for herpes simplex virus (HSV) infections is oral antiviral therapy with valacyclovir, famciclovir, or acyclovir, with valacyclovir 500 mg twice daily being the preferred option for most immunocompetent patients with genital herpes. 1, 2

Treatment Options by HSV Type

Genital HSV Infections

• First episode:

  • Valacyclovir 1 gram twice daily for 7-10 days 3
  • Famciclovir 250 mg three times daily for 7-10 days 2
  • Acyclovir 400 mg three times daily for 7-10 days 2

• Recurrent episodes:

  • Valacyclovir 500 mg twice daily for 3-5 days 3
  • Famciclovir 125 mg twice daily for 5 days 2
  • Acyclovir 400 mg three times daily for 5 days 2

• Suppressive therapy (for frequent recurrences - 6 or more per year):

  • Valacyclovir 500 mg daily (or 1 gram daily for patients with ≥10 outbreaks/year) 1, 3
  • Acyclovir 400 mg twice daily 2
  • Famciclovir 250 mg twice daily 2

Orolabial HSV (Cold Sores)

• Valacyclovir 2 grams twice daily for 1 day 3, 4
• Famciclovir 1500 mg as a single dose 4
• Acyclovir 400 mg five times daily for 5 days 2, 4

Mucocutaneous HSV in Immunocompromised Patients

• Acyclovir 5-10 mg/kg IV every 8 hours until clinical resolution for severe cases 1
• Oral therapy with higher doses: Acyclovir 400 mg 3-5 times daily until clinical resolution 1

Dosage Adjustments for Renal Impairment

Dosage adjustments are required for patients with renal impairment 1, 3:

Creatinine Clearance (mL/min)	Acyclovir Adjustment
>25	Normal dose
10-25	Normal dose every 8 hours
0-10	Normal dose every 12 hours

Management of Treatment Failure

If lesions do not begin to resolve within 7-10 days of treatment initiation, consider:

1. Viral resistance testing - Obtain viral culture and susceptibility testing 2
2. Alternative therapy - For acyclovir-resistant HSV:
   • IV foscarnet 40 mg/kg every 8 hours is the treatment of choice 2, 1, 5
   • Topical options for external lesions include trifluridine, cidofovir, or imiquimod (may require 21-28 days of application) 2, 5

Special Populations

HIV-Infected Patients

• Require longer courses of therapy (5-14 days)
• Short-course therapy (1-3 days) should not be used 2
• Higher doses may be needed for effective treatment 1
• Daily suppressive therapy may decrease HIV concentration in plasma and genital secretions 2

Pregnant Women

• Acyclovir is the preferred treatment due to its established safety profile in pregnancy 2, 1
• Episodic therapy can be offered for first-episode HSV disease and recurrences 2

Patient Education and Prevention

• Advise patients to abstain from sexual activity while lesions are present 1
• Educate about asymptomatic viral shedding and transmission risk 1
• Recommend consistent condom use during all sexual exposures 1
• For prevention of recurrent orolabial HSV, recommend sunscreen (SPF 15 or above) 4

Monitoring

• Re-examine patients 3-7 days after treatment initiation to assess response 1
• If no improvement occurs, consider alternative diagnoses, co-infection with other STIs, HIV infection, poor medication adherence, or antiviral resistance 1

Valacyclovir is often preferred over acyclovir due to better bioavailability and less frequent dosing, which improves patient adherence 3, 4. However, acyclovir remains a cost-effective option and is the preferred choice during pregnancy 2, 1.