What is the recommended treatment for Herpes Simplex Virus (HSV)?

Treatment of Herpes Simplex Virus (HSV)

For first-episode genital herpes, treat with oral antiviral therapy for 7-10 days using valacyclovir 1 g twice daily, famciclovir 250 mg three times daily, or acyclovir 400 mg three times daily. 1

First Clinical Episode

Genital Herpes

• Acyclovir 400 mg orally three times daily for 7-10 days is the recommended first-line treatment 1
• Alternative 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

Herpes Proctitis

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

Orolabial Herpes

• Valacyclovir 500 mg twice daily for 5 days initiated at first sign of outbreak 3
• Treatment is most effective when started during prodromal phase (tingling, burning, itching) or within 1 day of lesion onset 3

Recurrent Episodes

Episodic Therapy

For recurrent genital herpes, use shorter 5-day courses initiated during prodrome or within 1 day of lesion onset: 4

• Valacyclovir 500 mg orally twice daily for 5 days (preferred for convenience) 4
• Acyclovir 400 mg orally three times daily for 5 days 2, 4
• Acyclovir 800 mg orally twice daily for 5 days 2, 4
• Acyclovir 200 mg orally five times daily for 5 days 2, 4
• Famciclovir 125 mg orally twice daily for 5 days 4

Critical timing consideration: Episodic therapy is most effective when started during prodrome or within 1 day after lesion onset 4. Delayed treatment beyond 72 hours significantly reduces effectiveness 1, 3.

When Episodic Therapy May Not Be Beneficial

• Most immunocompetent patients with recurrent disease do not benefit substantially from episodic treatment since early administration is seldom achieved 2
• However, some patients experience limited benefit when treatment is instituted during prodrome or within 2 days of onset 2

Suppressive Therapy

All patients with recurrent HSV-2 should be offered daily suppressive therapy, which reduces recurrence frequency by ≥75%. 2, 4

Indications

• Patients with frequent recurrences (≥6 episodes per year) 2, 4, 3
• Patients seeking to reduce transmission risk to uninfected partners 2

Regimens

• Valacyclovir 1 g orally once daily 4
• Valacyclovir 500 mg orally once daily 4
• Acyclovir 400 mg orally twice daily 2, 4
• Famciclovir 250 mg orally twice daily 4

Important Considerations

• Suppressive therapy does not totally eliminate asymptomatic viral shedding or transmission potential 2
• Safety and efficacy documented for up to 5-6 years of continuous use 2, 4
• After 1 year of continuous suppressive therapy, consider discontinuation to reassess recurrence rate 2, 4
• Suppressive therapy reduces HSV-2 transmission to susceptible heterosexual partners by 50% 2
• However, suppressive therapy is NOT effective for reducing transmission among persons with HIV/HSV-2 coinfection 2

Severe Disease

For severe HSV requiring hospitalization (disseminated infection, encephalitis, pneumonitis, hepatitis), use IV acyclovir 5-10 mg/kg every 8 hours for 5-7 days or until clinical resolution. 2, 1, 5

Specific Severe Presentations

• Herpes simplex encephalitis: IV acyclovir 10 mg/kg every 8 hours for 10 days 5
• Neonatal herpes: IV acyclovir 10 mg/kg every 8 hours for 10 days 5
• Varicella-zoster in immunocompromised: IV acyclovir 500 mg/m² every 8 hours for 7 days 5

Special Populations

HIV-Infected/Immunocompromised Patients

• Treat orolabial lesions with oral valacyclovir, famciclovir, or acyclovir for 5-10 days 2
• Genital HSV should be treated for 5-14 days (NOT short-course 1-3 day therapy) 2
• Severe mucocutaneous HSV lesions respond best to initial IV acyclovir, then switch to oral therapy after lesions begin to regress 2
• Higher doses may be required: acyclovir 400 mg orally 3-5 times daily until clinical resolution 1, 3
• Famciclovir 500 mg twice daily has been effective in reducing recurrences and subclinical shedding 1

Acyclovir-Resistant HSV

• Suspect resistance if lesions do not begin to resolve within 7-10 days of therapy 2
• Obtain viral culture and susceptibility testing if resistance suspected 2
• IV foscarnet is the treatment of choice for acyclovir-resistant HSV 2
• Case reports suggest brincidofovir, imiquimod, and topical cidofovir may be useful 2
• Pritelivir (helicase-primase inhibitor) is being studied in open-label trials for immunocompromised patients with acyclovir-resistant infections 2

Pregnancy

• Antiviral prophylaxis with acyclovir recommended from 36 weeks gestation until delivery in women with history of genital herpes 6, 7
• Elective cesarean delivery should be performed in laboring patients with active lesions to reduce neonatal herpes risk 6, 7

Geriatric Patients

• Acyclovir plasma concentrations are higher in geriatric patients due to age-related renal function changes 5
• Dosage reduction may be required in patients with underlying renal impairment 5

Critical Pitfalls to Avoid

• Never use topical acyclovir alone - it is substantially less effective than oral therapy and its use is discouraged 2, 4, 3
• Do not delay treatment - effectiveness significantly reduced if initiated beyond 72 hours after symptom onset 1, 3
• Do not use short-course (1-3 day) therapy in HIV-infected patients 2
• Do not forget to counsel about asymptomatic viral shedding - transmission can occur during periods without visible lesions 2, 4
• Do not fail to offer suppressive therapy to patients with frequent recurrences (≥6 episodes/year) 2, 4, 3

Patient Counseling

Essential Education Points

• Patients should abstain from sexual activity while lesions are present 2
• Emphasize potential for recurrent episodes, asymptomatic viral shedding, and sexual transmission 2
• Sexual transmission documented during periods without evidence of lesions 2
• Encourage consistent condom use during all sexual exposures 2
• Antiviral medications control symptoms but do not eradicate the virus or prevent all recurrences 4, 3
• Women of childbearing age should inform healthcare providers about HSV infection during pregnancy 2

Partner Management

• Sex partners should be evaluated and counseled 2
• Symptomatic partners managed same as any patient with genital lesions 2
• Asymptomatic partners should be queried about typical and atypical genital lesions 2
• HSV-2-seronegative HIV-infected persons should ask partners to undergo type-specific serologic testing before initiating sexual activity 2

Monitoring

• No laboratory monitoring needed for patients receiving episodic or suppressive therapy unless substantial renal impairment present 2, 1
• For patients receiving high-dose IV acyclovir, monitor renal function at initiation and once or twice weekly during treatment 2
• Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome reported with high-dose (8 g/day) valacyclovir but not at standard HSV treatment doses 2