What is the recommended treatment for a typical adult with oral (labial) HSV‑1 infection?

Treatment of Oral Herpes (Herpes Labialis)

For typical adults with oral HSV-1 infection (cold sores), initiate valacyclovir 2 g twice daily for 1 day (doses separated by 12 hours) at the first sign of prodromal symptoms or within 24 hours of lesion onset. 1

First-Line Episodic Treatment Options

Valacyclovir 2 g twice daily for 1 day is the preferred first-line regimen, reducing median episode duration by approximately 1 day compared to placebo, with high-quality evidence supporting its efficacy. 1 This short-course, high-dose approach offers superior convenience and adherence compared to traditional longer regimens. 1

Alternative oral antiviral regimens include:

• Famciclovir 1500 mg as a single dose provides comparable efficacy to valacyclovir with the convenience of single-day dosing. 1, 2
• Acyclovir 400 mg five times daily for 5 days remains effective but requires more frequent dosing, which may reduce patient adherence. 1

All three oral antivirals are generally well-tolerated, with common side effects including headache (<10%), nausea (<4%), and diarrhea, typically mild to moderate in intensity. 1

Critical Timing Considerations

Treatment must be initiated during the prodromal phase (tingling, burning, itching) or within 24 hours of lesion appearance to achieve maximal benefit, because peak HSV-1 viral titers occur in the first 24 hours after lesions develop. 1 Starting therapy after this window markedly diminishes clinical efficacy and reduces symptom relief. 1 Patient-initiated therapy at first symptoms may even prevent lesion development in some cases. 1

Provide patients with a prescription to keep on hand so treatment can begin immediately when prodromal symptoms appear. 1

Topical Therapy: Not Recommended as Primary Treatment

Topical antivirals provide only modest clinical benefit and are substantially less effective than oral therapy for herpes labialis. 1 Relying solely on topical treatments when oral therapy is available represents a common pitfall that should be avoided. 1

Suppressive Therapy for Frequent Recurrences

Consider daily suppressive therapy for patients experiencing six or more recurrences per year, those with particularly severe or complicated disease, or those with significant psychological distress from recurrences. 1

Suppressive therapy options include:

• 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

Daily suppressive therapy reduces recurrence frequency by ≥75% among patients with frequent episodes. 1 Safety and efficacy have been documented for acyclovir for up to 6 years, and for valacyclovir and famciclovir for 1 year of continuous use. 1 After 1 year of continuous suppressive therapy, consider discontinuation to reassess the patient's recurrence rate, as frequency decreases over time in many patients. 1

Important limitation: Suppressive therapy reduces but does not eliminate asymptomatic viral shedding, so transmission risk persists even on daily antivirals. 1

Special Populations

Immunocompromised Patients

Episodes are typically longer and more severe in immunocompromised patients, potentially involving the entire oral cavity or extending across the face. 1 These patients may require higher doses or longer treatment durations. 1

Acyclovir resistance rates are substantially higher in immunocompromised individuals (approximately 7%) compared to immunocompetent hosts (<0.5%). 1 Despite increasing use of HSV-specific antivirals, resistance remains rare in the general population. 1

Severe Intraoral HSV or Gingivostomatitis

For mild symptomatic gingivostomatitis, use acyclovir 20 mg/kg (maximum 400 mg/dose) orally three times daily for 5–10 days. 1

For moderate to severe gingivostomatitis requiring hospitalization, initiate acyclovir 5–10 mg/kg IV three times daily until lesions begin to regress, then switch to oral acyclovir and continue until lesions completely heal. 1

Acyclovir-Resistant HSV

For confirmed acyclovir-resistant HSV infection, foscarnet 40 mg/kg IV three times daily is the treatment of choice. 1 Resistance rates remain below 0.5% in immunocompetent hosts. 1

Renal Impairment

Dose adjustments are mandatory for patients with renal impairment to prevent drug accumulation and neurotoxicity. 1 In patients aged ≥80 years, assess renal function (creatinine clearance) before initiating any oral antiviral. 1

Preventive Counseling

Counsel patients to identify and avoid personal triggers, including:

• Ultraviolet light exposure: Apply sunscreen (SPF 15 or higher) or zinc oxide to decrease UV-triggered recurrences. 1, 3
• Fever, psychological stress, and menstruation 1

Patients remain contagious until all lesions are fully crusted, which is the standard clinical endpoint indicating substantial reduction in transmission risk. 1 Even with optimal antiviral therapy, viral shedding persists for approximately 6.4 days with valacyclovir (compared to 8.1 days without treatment). 1 Avoid direct contact (kissing, sharing utensils, towels, lip balm) until complete crusting occurs. 1

Common Pitfalls to Avoid

• Do not rely solely on topical treatments when oral antivirals are more effective. 1
• Do not start treatment too late—efficacy decreases significantly when initiated after the first 24 hours. 1
• Do not use inadequate dosing—short-course, high-dose therapy is more effective than traditional longer courses at lower doses. 1
• Do not fail to consider suppressive therapy in patients with ≥6 recurrences per year who could significantly benefit. 1
• Do not forget to discuss triggers (UV exposure, stress, fever) that patients should avoid even while on suppressive therapy. 1