What is the recommended treatment for herpes simplex infection?

Treatment of Herpes Simplex Virus Infection

Acyclovir is the treatment of choice for herpes simplex virus infections, with dosing regimens varying based on clinical presentation, severity, and patient factors. 1, 2

First Clinical Episode Treatment

• For first episodes of genital herpes, recommended regimens include:

  • Acyclovir 400 mg orally three times daily for 7-10 days 2
  • Acyclovir 200 mg orally five times daily for 7-10 days 1, 2
  • Valacyclovir 1 g orally twice daily for 7-10 days 2
  • Famciclovir 250 mg orally three times daily for 7-10 days 2

• For herpes proctitis, higher dosages are required:

  • Acyclovir 400 mg orally five times daily for 10 days or until clinical resolution 1, 2

Recurrent Episodes Treatment

• For recurrent genital herpes episodes, shorter courses are effective:

  • Acyclovir 400 mg orally three times daily for 5 days 2
  • Acyclovir 800 mg orally twice daily for 5 days 2
  • Acyclovir 800 mg orally three times daily for 2 days 3
  • Valacyclovir 500 mg twice daily for 3-5 days 4

• Treatment should be initiated at the first sign of prodrome or within 1-2 days of lesion onset for maximum effectiveness 1, 2

Suppressive Therapy

• For patients with frequent recurrences (≥6 per year), suppressive therapy is recommended:

  • Acyclovir 400 mg orally twice daily 1, 2, 5
  • Valacyclovir 500 mg once daily 2
  • Valacyclovir 1 g once daily for patients with ≥10 recurrences per year 2
  • Famciclovir 250 mg twice daily 5

• Suppressive therapy reduces frequency of recurrences by ≥75% and reduces asymptomatic viral shedding 2, 5

Herpes Simplex Encephalitis

• For herpes simplex encephalitis, immediate treatment is critical to reduce mortality:

  • Acyclovir 10 mg/kg intravenously every 8 hours for 14-21 days in adults and children with normal renal function 1
  • Acyclovir 20 mg/kg intravenously every 8 hours for 21 days in neonates 1, 6

• Early treatment (within 4 days of symptom onset) reduces mortality from 28% to 8% 1

• Consider repeating CSF PCR for HSV at the end of therapy in patients without appropriate clinical response; continue treatment if positive 1

Special Populations

Immunocompromised Patients

• Immunocompromised patients may require longer courses of therapy and closer monitoring 1, 2
• For severe HSV infections in immunocompromised patients:
  • Acyclovir 5-10 mg/kg intravenously every 8 hours 6
  • Consider foscarnet for acyclovir-resistant infections 1, 7

Neonatal HSV

• For neonatal herpes infections:
  • Acyclovir 20 mg/kg intravenously every 8 hours for 21 days 1, 6
  • Higher-dose regimen has decreased mortality to 5% 1

Important Clinical Considerations

• Topical acyclovir is substantially less effective than oral therapy and is not recommended 1, 2

• Antiviral medications do not eradicate latent virus or affect the risk of recurrences after treatment is discontinued 1, 2

• For herpes labialis (cold sores), valacyclovir and famciclovir offer improved bioavailability and convenient dosing schedules compared to acyclovir, but are more expensive 5, 4

• Relapse of herpes simplex encephalitis can occur after completion of therapy (rates up to 5%), particularly with shorter treatment courses 1

• For severe HSV disease during immunomodulator therapy, antiviral therapy should be initiated and immunomodulators discontinued until symptoms improve 1

Common Pitfalls and Caveats

• Delayed initiation of therapy for herpes simplex encephalitis (>4 days after symptom onset) is associated with significantly higher mortality and should be avoided 1

• Resistance to acyclovir is rare in immunocompetent individuals but can occur in immunocompromised patients, particularly those with HIV infection 7, 8

• Valacyclovir and famciclovir have better oral bioavailability than acyclovir, allowing for less frequent dosing, but acyclovir remains an effective and often less expensive option 5, 7

• Treatment of recurrent orolabial herpes has limited evidence of benefit as these episodes tend to be mild and infrequent in immunocompetent hosts 5