What is the recommended treatment for an active HSV‑1 labial (cold‑sore) outbreak, including first‑line topical antivirals, oral therapy for extensive disease, and suppressive regimens?

Treatment of HSV-1 Labialis (Cold Sores)

For an active cold sore outbreak, initiate oral valacyclovir 2 g twice daily for 1 day or famciclovir 1500 mg as a single dose at the earliest sign of symptoms—ideally during the prodromal phase or within 24 hours of lesion onset. 1

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First-Line Episodic Treatment

Oral antiviral therapy is superior to topical agents and should be the standard of care for active outbreaks. 1

Preferred Regimens (Immunocompetent Adults)

• Valacyclovir 2 g twice daily for 1 day (12 hours apart) reduces median episode duration by approximately 1 day and offers the most convenient dosing schedule. 1
• Famciclovir 1500 mg as a single oral dose provides equivalent efficacy with single-day dosing. 1, 2
• Acyclovir 400 mg orally five times daily for 5 days remains effective but requires more frequent dosing, which may reduce adherence. 1

Critical Timing

• Peak viral titers occur in the first 24 hours after lesion onset, making early initiation essential to block viral replication and achieve maximal benefit. 1
• Efficacy decreases significantly when treatment starts after the first 24 hours or once lesions are fully developed. 1
• Patient-initiated therapy at the first sign of prodromal symptoms (tingling, burning, itching) may even prevent lesion development in some cases. 1

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Topical Therapy (Less Effective Alternative)

Topical antivirals provide only modest clinical benefit and are substantially less effective than oral therapy. 1

• Acyclovir 5% cream applied five times daily for 5 days may shorten lesion duration by approximately 1 day if applied during the prodrome, but is not recommended as first-line therapy. 1, 3, 4
• Penciclovir 1% cream has demonstrated superiority over acyclovir cream in some studies, with prolonged intracellular half-life, but remains inferior to oral antivirals. 5, 6
• Topical agents cannot reach the site of viral reactivation and are not effective for suppressive therapy. 1

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Suppressive Therapy for Frequent Recurrences

Patients experiencing six or more recurrences per year should be offered daily suppressive therapy, which reduces recurrence frequency by ≥75%. 1

First-Line Suppressive Regimens

• Valacyclovir 500 mg once daily (can increase to 1000 mg once daily for very frequent recurrences). 1
• Famciclovir 250 mg twice daily. 1
• Acyclovir 400 mg twice daily. 1, 4

Duration and Monitoring

• Safety and efficacy have been documented for acyclovir for up to 6 years; valacyclovir and famciclovir have documented safety for 1 year of continuous use. 1
• After 1 year of continuous suppressive therapy, consider a trial off therapy to reassess recurrence frequency, as it decreases over time in many patients. 1
• Suppressive therapy reduces but does not eliminate asymptomatic viral shedding, so transmission risk persists even without visible lesions. 1

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Special Populations

Immunocompromised Patients

• Episodes are typically longer and more severe, potentially involving the oral cavity or extending across the face, and may require higher doses or longer treatment durations. 1
• Acyclovir resistance rates are higher in immunocompromised patients (7% versus <0.5% in immunocompetent hosts). 1
• For severe intraoral HSV or gingivostomatitis requiring hospitalization, use acyclovir 5–10 mg/kg IV every 8 hours until lesions begin to regress, then switch to oral therapy. 1
• For confirmed acyclovir-resistant HSV, foscarnet 40 mg/kg IV three times daily is the treatment of choice. 1

HIV-Infected Patients

• For recurrent orolabial herpes in HIV-infected adults, famciclovir 500 mg twice daily for 7 days is FDA-approved. 2

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Preventive Counseling and Trigger Avoidance

Patients should identify and avoid personal triggers to reduce outbreak frequency. 1

• Ultraviolet light exposure: Apply sunscreen (SPF 15 or higher) or zinc oxide to the lips before sun exposure to prevent UV-triggered recurrences. 1, 4
• Other common triggers include fever, psychological stress, and menstruation. 1

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Contagiousness and Transmission Risk

• Active vesicular and ulcerative lesions are highly contagious; patients should avoid direct contact (e.g., kissing) and sharing items that contact the mouth. 1
• Patients remain contagious until all lesions are fully crusted, which is the standard clinical endpoint indicating substantial reduction in transmission risk. 1
• Valacyclovir started within 24 hours of symptom onset shortens the time to HSV PCR clearance from lesions by approximately 21% (mean 6.4 days with valacyclovir vs. 8.1 days with placebo). 1
• Asymptomatic shedding can occur even during suppressive therapy, so partners should be counseled that zero transmission risk does not exist. 1

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Common Pitfalls to Avoid

• Relying solely on topical treatments when oral therapy is more effective. 1
• Starting treatment too late (after the first 24 hours or once lesions are fully developed). 1
• Failing to consider suppressive therapy in patients with ≥6 recurrences per year who could significantly benefit. 1
• Not discussing trigger avoidance (UV light, stress, fever) even while on suppressive therapy. 1

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Safety and Tolerability

• All oral antivirals (acyclovir, valacyclovir, famciclovir) are generally well-tolerated with minimal adverse events. 1
• Common side effects include headache (<10%), nausea (<4%), and diarrhea, which are typically mild to moderate in intensity. 1
• Despite increasing use of HSV-specific antiviral agents, the incidence of resistant HSV-1 strains remains low (<0.5% in immunocompetent hosts). 1