What is the recommended treatment for herpes simplex?

Treatment of Herpes Simplex Virus Infection

Oral antiviral therapy with acyclovir, valacyclovir, or famciclovir is the recommended treatment for herpes simplex virus infections, with specific regimens determined by clinical presentation (first episode, recurrent episode, or suppressive therapy), anatomic location, and immune status. 1, 2, 3

First Clinical Episode

For initial genital herpes episodes, treat with acyclovir 400 mg orally three times daily for 7-10 days, or alternative regimens including acyclovir 200 mg five times daily, valacyclovir 1 g twice daily, or famciclovir 250 mg three times daily for 7-10 days. 1, 3

• Extend treatment beyond 10 days if healing remains incomplete 3
• For herpes proctitis or severe oral infection, increase acyclovir to 400 mg five times daily for 10 days or until clinical resolution 1, 3

Recurrent Episodes

Initiate treatment at the first sign of prodrome or within 1-2 days of lesion onset for maximum effectiveness. 1, 3

Genital Herpes Recurrences

• Acyclovir 400 mg three times daily for 5 days 1, 3
• Acyclovir 800 mg twice daily for 5 days 3
• Acyclovir 800 mg three times daily for 2 days 3
• Valacyclovir 500 mg twice daily for 3-5 days 4

Orolabial Herpes (Cold Sores)

For cold sores, use high-dose, short-course therapy: valacyclovir 2 g twice daily for 1 day, which reduces episode duration by approximately 1 day compared to placebo. 2, 3, 4

• Alternative: famciclovir 1500 mg as a single dose or 750 mg twice daily for 1 day 2, 3
• Traditional regimen: acyclovir 400 mg five times daily for 5 days (less convenient dosing) 2
• Peak viral titers occur within the first 24 hours after lesion onset, making early intervention critical 2

Suppressive Therapy

For patients with ≥6 recurrences per year, initiate daily suppressive therapy, which reduces recurrence frequency by ≥75%. 1, 2, 3

Recommended Regimens

• Acyclovir 400 mg twice daily 1, 2, 3
• Valacyclovir 500 mg once daily (increase to 1 g daily for ≥10 recurrences per year) 2, 3
• Famciclovir 250 mg twice daily 2

Duration and Monitoring

• Safety documented for acyclovir up to 6 years; valacyclovir and famciclovir for 1 year 2, 3
• After 1 year of continuous suppressive therapy, consider discontinuation to reassess recurrence frequency, as it decreases over time in many patients 2
• Among immunocompetent adults on valacyclovir 1 g daily, 55% remained recurrence-free at 6 months and 34% at 12 months 4

Life-Threatening Infections

Herpes Simplex Encephalitis

Administer acyclovir 10 mg/kg intravenously every 8 hours for 14-21 days immediately upon suspicion—do not delay for diagnostic confirmation. 1

• Early treatment (within 4 days of symptom onset) reduces mortality from 28% to 8% 1
• Relapse occurs in up to 5% of cases, particularly with shorter treatment courses 1

Neonatal HSV

• Acyclovir 20 mg/kg intravenously every 8 hours for 21 days 1
• This higher-dose regimen has decreased mortality to 5% 1

Special Populations

Immunocompromised Patients

• Require longer treatment courses and closer monitoring 1, 3
• Acyclovir resistance rates reach 7% in immunocompromised patients versus <0.5% in immunocompetent hosts 2
• Episodes are typically longer, more severe, and may involve extensive facial or oral cavity involvement 2
• Among HIV-infected adults on stable antiretroviral therapy, valacyclovir 500 mg twice daily for 6 months resulted in 65% remaining recurrence-free versus 26% on placebo 4

Acyclovir-Resistant HSV

For confirmed acyclovir-resistant infection, switch to foscarnet 40 mg/kg intravenously three times daily. 2

Critical Clinical Considerations

What NOT to Do

• Do not use topical acyclovir—it is substantially less effective than oral therapy and cannot reach the site of viral reactivation 1, 2, 3
• Do not delay treatment initiation; efficacy decreases significantly when started after lesions fully develop 2
• Do not rely on episodic treatment alone for patients with ≥6 recurrences per year who would benefit from suppression 2

Important Counseling Points

• Antiviral medications do not eradicate latent virus or affect recurrence risk after discontinuation 1, 3
• Suppressive therapy reduces but does not eliminate asymptomatic viral shedding 2
• Patients should identify and avoid personal triggers including UV light exposure, stress, fever, and menstruation 2
• Patient-initiated therapy at earliest symptoms may prevent lesion development in some cases 2

Safety Profile

• Common adverse events include nausea (2.7-4.8%), diarrhea (2.4%), and headache, which are typically mild to moderate 2, 5
• All oral antivirals are generally well-tolerated with minimal adverse events 2
• Serious neurologic adverse events (agitation, confusion, encephalopathy, seizures) may occur, particularly in older adults or those with renal impairment 5