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

Treatment of Herpes Simplex Virus (HSV)

For first-episode genital herpes, treat with oral valacyclovir 1 g twice daily, acyclovir 400 mg three times daily, or famciclovir 250 mg three times daily for 7-10 days; for recurrent episodes, use shorter 5-day courses initiated at first sign of symptoms; and offer daily suppressive therapy to all patients with HSV-2 who have frequent recurrences (≥6 episodes/year). 1

First Clinical Episode

The CDC recommends oral antiviral therapy for 7-10 days as the cornerstone of initial HSV treatment. 1 The preferred regimens include:

• Acyclovir 400 mg orally three times daily for 7-10 days is the recommended first-line treatment 1
• Valacyclovir 1 g orally twice daily for 7-10 days offers equivalent efficacy with more convenient dosing 1
• Famciclovir 250 mg orally three times daily for 7-10 days is an equally effective alternative 1
• Acyclovir 200 mg orally five times daily for 7-10 days can be used but requires more frequent dosing 1

Site-specific considerations:

• For herpes proctitis, use acyclovir 400 mg orally five times daily for 10 days or until clinical resolution 1
• For orolabial herpes, valacyclovir 500 mg twice daily for 5 days initiated at first sign of outbreak is recommended 1

Recurrent Episodes

The CDC recommends shorter 5-day courses of antiviral therapy for recurrent genital herpes, with treatment most effective when started during prodrome or within 1 day of lesion onset. 1, 2

Preferred episodic treatment options:

• Valacyclovir 500 mg orally twice daily for 5 days is preferred due to convenience 1, 2
• Acyclovir 400 mg orally three times daily for 5 days 1, 2
• Acyclovir 800 mg orally twice daily for 5 days 1, 2
• Famciclovir 125 mg orally twice daily for 5 days 1, 2

Research supports even shorter courses: a 2-day regimen of acyclovir 800 mg three times daily significantly reduced lesion duration (4 vs 6 days), episode duration, and viral shedding compared to placebo, offering a convenient alternative. 3

Suppressive Therapy

The CDC recommends offering daily suppressive therapy to all patients with recurrent HSV-2, which reduces recurrence frequency by ≥75%. 1, 2

Clear indications for suppressive therapy include:

• Patients with frequent recurrences (≥6 episodes per year) 1, 2
• Patients seeking to reduce transmission risk to uninfected partners 1, 2

Suppressive regimens:

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

Suppressive therapy is safe for up to 6 years with acyclovir and 1 year with valacyclovir. 2 After 1 year of suppressive therapy, consider discontinuation to reassess recurrence frequency. 2

Special Populations

HIV-infected/immunocompromised patients:

• Treat orolabial lesions with oral valacyclovir, famciclovir, or acyclovir for 5-10 days 1
• Treat genital HSV for 5-14 days 1
• Higher doses may be required: acyclovir 400 mg orally 3-5 times daily until clinical resolution 4

Severe disease requiring hospitalization:

• Acyclovir 5-10 mg/kg IV every 8 hours for 5-7 days or until clinical resolution 4, 5
• IV acyclovir is indicated for herpes simplex encephalitis, neonatal herpes, and severe mucocutaneous HSV in immunocompromised patients 5

Acyclovir-resistant HSV:

• IV foscarnet is the treatment of choice 1

Pregnancy:

• Antiviral prophylaxis with acyclovir is recommended from 36 weeks of gestation until delivery in women with a 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

Critical Clinical Considerations

Common pitfalls to avoid:

• Topical acyclovir is substantially less effective than systemic treatment and should not be used 4, 2
• Delaying treatment beyond 72 hours significantly reduces effectiveness 4
• Failing to consider suppressive therapy in patients with frequent recurrences 4

Patient counseling essentials:

• Abstain from sexual activity while lesions are present 1, 2
• Use consistent condom use during all sexual exposures with new or uninfected partners 1, 2
• Inform patients about potential for recurrent episodes, asymptomatic viral shedding, and sexual transmission 1, 2
• Genital herpes is a recurrent, incurable viral disease; antivirals control symptoms but do not eradicate the virus 2

Monitoring:

• No laboratory monitoring is needed for patients receiving episodic or suppressive therapy unless substantial renal impairment is present 1, 4
• Dosage reduction may be required in geriatric patients with underlying renal impairment 5