What is the treatment for a Herpes Simplex Virus (HSV) flare-up?

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Last updated: December 17, 2025View editorial policy

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Treatment for HSV Flare-Up

For recurrent HSV flare-ups, treat with oral valacyclovir 500 mg twice daily for 5 days, initiated at the first sign of prodrome or within 24 hours of lesion onset. 1, 2, 3

First-Line Treatment Options for Recurrent Episodes

The CDC recommends several equivalent oral antiviral regimens for recurrent HSV episodes, all administered for 5 days: 4, 1, 2, 3

  • Valacyclovir 500 mg twice daily (preferred due to convenient dosing) 2, 3
  • Acyclovir 400 mg three times daily 1, 2, 3
  • Acyclovir 800 mg twice daily 1, 2, 3
  • Famciclovir 125 mg twice daily 2, 3

Timing is critical: Treatment must be started during the prodrome or within 1 day of lesion onset to achieve maximum benefit. 2, 3 When initiated early, these regimens reduce lesion duration from a median of 6 days to 4 days and decrease viral shedding time from approximately 58 hours to 25 hours. 5

When to Consider Suppressive Therapy

If you experience 6 or more recurrences per year, switch to daily suppressive therapy rather than episodic treatment. 1, 2, 3 Suppressive therapy reduces recurrence frequency by at least 75% and decreases asymptomatic viral shedding. 4, 1, 3

Recommended suppressive regimens include: 1, 2, 3

  • Valacyclovir 1 gram once daily (most convenient)
  • Valacyclovir 500 mg once daily (alternative)
  • Acyclovir 400 mg twice daily
  • Famciclovir 250 mg twice daily

Suppressive therapy is safe for up to 6 years with acyclovir and at least 1 year with valacyclovir. 2 After 1 year of continuous suppression, consider discontinuing to reassess your natural recurrence frequency. 4, 2

Special Populations and Situations

Immunocompromised Patients

If you are HIV-infected or otherwise immunocompromised, use higher doses and longer treatment duration: acyclovir 400 mg orally 3-5 times daily for 5-14 days, or consider intravenous therapy for severe disease. 1, 3 These patients may experience prolonged episodes with extensive disease and are at higher risk for acyclovir-resistant strains. 4

Severe Disease Requiring Hospitalization

For severe HSV disease or complications, administer intravenous acyclovir 5-10 mg/kg every 8 hours for 5-7 days or until clinical improvement. 1, 3

Acyclovir-Resistant HSV

If lesions fail to improve within 7-10 days of appropriate antiviral therapy, suspect acyclovir resistance. 2, 6 In this case, switch to foscarnet 40 mg/kg IV three times daily or 60 mg/kg IV twice daily as the treatment of choice. 1, 6 Resistance is rare in immunocompetent patients but occurs more frequently in immunocompromised hosts with frequent, severe reactivations. 6

Critical Pitfalls to Avoid

Never use topical acyclovir - it is substantially less effective than oral therapy and is strongly discouraged by the CDC. 2, 3

Do not delay treatment - the benefit of episodic therapy is maximized only when started during prodrome or within 1 day of lesion onset. 2, 3 Most immunocompetent patients with recurrent disease receive limited benefit if treatment is delayed beyond this window. 4

Avoid valacyclovir 8 grams per day in immunocompromised patients due to risk of hemolytic uremic syndrome/thrombotic thrombocytopenic purpura. 2

Patient Counseling Points

Counsel patients that: 2, 3

  • HSV is a chronic, incurable viral infection with potential for recurrent episodes
  • Antiviral medications control symptoms but do not eradicate latent virus
  • Asymptomatic viral shedding can occur, allowing transmission even without visible lesions
  • Abstain from sexual activity when lesions or prodromal symptoms are present
  • Use condoms consistently during all sexual exposures with new or uninfected partners
  • Inform sexual partners about HSV status

Monitoring Requirements

No laboratory monitoring is needed for patients on episodic or suppressive therapy unless substantial renal impairment is present. 3 Acyclovir is primarily renally excreted and requires dose adjustment in renal insufficiency. 1

References

Guideline

Aciclovir Dosage for HSV and VZV Infections

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Treatment for Recurrent Genital Herpes

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Treatment of Herpes Simplex Virus (HSV)

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Two-day regimen of acyclovir for treatment of recurrent genital herpes simplex virus type 2 infection.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2002

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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