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 per year). 1

First Clinical Episode

The CDC recommends oral antiviral therapy for 7-10 days as the cornerstone of initial HSV treatment 1. The three equivalent first-line options are:

• Acyclovir 400 mg orally three times daily for 7-10 days (preferred first-line) 1
• Valacyclovir 1 g orally twice daily for 7-10 days 1
• Famciclovir 250 mg orally three times daily for 7-10 days 1

Alternative dosing includes acyclovir 200 mg orally five times daily for 7-10 days, though this requires more frequent administration 1. For orolabial herpes specifically, use valacyclovir 500 mg twice daily for 5 days initiated at the first sign of outbreak 1. For herpes proctitis, extend acyclovir to 400 mg orally five times daily for 10 days or until clinical resolution 1.

Critical timing consideration: Treatment should be initiated within 72 hours of symptom onset for optimal effectiveness 2. Delaying beyond this window significantly reduces treatment efficacy 2.

Recurrent Episodes

For recurrent genital herpes, the CDC recommends 5-day courses of antiviral therapy started during prodrome or within 1 day of lesion onset 1, 3. This shorter duration is equally effective for recurrences and improves patient convenience:

• Valacyclovir 500 mg orally twice daily for 5 days (preferred for convenience) 1, 3
• Acyclovir 400 mg orally three times daily for 5 days 1, 3
• Acyclovir 800 mg orally twice daily for 5 days 1, 3
• Famciclovir 125 mg orally twice daily for 5 days 1, 3

Research supports even shorter regimens: a 2-day course of acyclovir 800 mg three times daily significantly reduced lesion duration (4 days versus 6 days with placebo), episode duration, and viral shedding, while increasing the proportion of aborted episodes 4. High-dose single-day regimens (famciclovir 1000 mg twice daily) have also demonstrated efficacy 5.

Suppressive Therapy

The CDC recommends offering daily suppressive therapy to all patients with recurrent HSV-2, which reduces recurrence frequency by ≥75% 1, 3. This is particularly important for:

• Patients with frequent recurrences (≥6 episodes per year) 1, 3
• Patients seeking to reduce transmission risk to uninfected partners 1

Suppressive regimens include:

• Valacyclovir 1 g orally once daily (only antiviral FDA-approved for once-daily dosing) 1, 3, 6
• Valacyclovir 500 mg orally once daily 1, 3
• Acyclovir 400 mg orally twice daily 1, 3
• Famciclovir 250 mg orally twice daily 1, 3

Suppressive therapy is safe for up to 6 years with acyclovir and 1 year with valacyclovir 3. After 1 year of suppressive therapy, consider discontinuation to reassess recurrence frequency 3.

Severe Disease and Special Populations

For severe initial genital herpes requiring hospitalization or HSV encephalitis, use IV acyclovir 5-10 mg/kg every 8 hours 2, 7. IV acyclovir is FDA-indicated for severe initial genital herpes episodes, herpes simplex encephalitis, neonatal HSV infections, and HSV in immunocompromised patients 7.

For HIV-infected or immunocompromised patients:

• Treat orolabial lesions with oral valacyclovir, famciclovir, or acyclovir for 5-10 days 1
• Treat genital HSV for 5-14 days 1
• Use higher doses: acyclovir 400 mg orally 3-5 times daily until clinical resolution 2
• Famciclovir 500 mg twice daily reduces recurrences and subclinical shedding in HIV-infected patients 2

For acyclovir-resistant HSV (suspect if lesions do not resolve within 7-10 days of therapy), IV foscarnet 40 mg/kg every 8 hours is the treatment of choice 1, 3.

Critical Pitfalls to Avoid

• Never use topical acyclovir alone—it is substantially less effective than systemic treatment 2, 3
• Avoid valacyclovir 8 g/day in immunocompromised patients—associated with hemolytic uremic syndrome/thrombotic thrombocytopenic purpura 3
• Do not delay treatment beyond 72 hours—significantly reduces effectiveness 2
• Adjust doses in geriatric patients with renal impairment—acyclovir plasma concentrations are higher due to age-related renal changes 7
• Consider probenecid interactions—coadministration increases acyclovir half-life and reduces renal clearance 7

Patient Counseling Requirements

Patients must be counseled about 1, 3:

• Abstain from sexual activity when lesions or prodromal symptoms are present 1, 3
• Use consistent condom use during all sexual exposures with new or uninfected partners 1, 3
• Asymptomatic viral shedding can occur, potentially leading to transmission 1, 3
• Genital herpes is recurrent and incurable—antivirals control symptoms but do not eradicate the virus 3
• Inform sex partners about having genital herpes 3

Monitoring

No laboratory monitoring is needed for patients receiving episodic or suppressive therapy unless substantial renal impairment is present 1, 2. For patients with persistent symptoms beyond 5 days of treatment, consider extended treatment and evaluate for potential co-infections 3.