How should oral herpes (herpes simplex virus‑1 infection) be treated in an adult, including dosing for primary and recurrent episodes and modifications for immunocompromised patients, pregnancy, frequent recurrences, and renal impairment?

Treatment of Oral Herpes (HSV-1) in Adults

For immunocompetent adults with oral herpes, treat with oral valacyclovir, famciclovir, or acyclovir for 5-10 days, starting therapy as early as possible—ideally during the prodrome or within 24 hours of lesion onset. 1

Primary Episode Treatment

For first-episode oral HSV-1 infection:

• Valacyclovir 1 g orally twice daily for 7-10 days is the preferred first-line regimen 1
• Acyclovir 400 mg orally three times daily for 7-10 days is an effective alternative 1
• Famciclovir 250 mg orally three times daily for 7-10 days is another option 2
• Extend treatment beyond 10 days if healing is incomplete 2, 1

For severe mucocutaneous disease requiring hospitalization:

• Start IV acyclovir 5-10 mg/kg every 8 hours until lesions begin to regress 2, 3
• Switch to oral therapy once improvement occurs and continue until complete healing 2
• Monitor renal function at initiation and once or twice weekly during IV treatment 2

Recurrent Episode Treatment

Timing is critical—peak viral replication occurs in the first 24 hours, so early intervention is essential for maximum benefit. 1, 3

Short-course, high-dose regimens (preferred for convenience and adherence):

• Valacyclovir 2 g orally twice daily for 1 day (doses 12 hours apart) reduces episode duration by approximately 1 day 1, 3
• Famciclovir 1500 mg as a single oral dose provides comparable efficacy 3, 4

Standard episodic regimens:

• Valacyclovir 500 mg orally twice daily for 5 days 1, 5
• Acyclovir 400 mg orally three times daily for 5 days 1, 5
• Acyclovir 800 mg orally twice daily for 5 days 5
• Famciclovir 125 mg orally twice daily for 5 days 1, 5

Provide patients with a prescription to keep on hand so treatment can be initiated immediately at first symptoms or prodrome. 1, 5

Suppressive Therapy for Frequent Recurrences

Consider daily suppressive therapy for patients with ≥6 recurrences per year—this reduces recurrence frequency by ≥75%. 1, 3

Suppressive regimens:

• Valacyclovir 500 mg orally once daily (may increase to 1000 mg once daily for very frequent recurrences) 3
• Acyclovir 400 mg orally twice daily 1, 3
• Famciclovir 250 mg orally twice daily 3

Duration and monitoring:

• Acyclovir has documented safety for up to 6 years of continuous use 1, 3
• Valacyclovir and famciclovir have documented safety for 1 year of continuous use 3
• After 1 year of suppressive therapy, consider discontinuation to reassess recurrence frequency, as episodes often decrease over time 1, 3

Immunocompromised Patients (Including HIV-Infected)

HIV-infected and other immunocompromised patients require longer treatment courses and should not receive short-course therapy. 2

For orolabial lesions:

• Oral valacyclovir, famciclovir, or acyclovir for 5-10 days 2
• For severe mucocutaneous lesions, start with IV acyclovir and switch to oral therapy after lesions begin to regress 2
• Continue therapy until lesions have completely healed 2

For HIV-infected patients with recurrent orolabial herpes:

• Famciclovir 500 mg orally twice daily for 7 days 2
• Episodes are typically longer and more severe, potentially involving the oral cavity or extending across the face 1, 3
• Acyclovir resistance rates are higher (7% versus <0.5% in immunocompetent patients) 1, 3

For suppressive therapy in HIV-infected patients:

• Use twice-daily regimens: valacyclovir 500 mg twice daily, or acyclovir/famciclovir twice daily 2
• Once-daily regimens are less effective in this population 2

Treatment Failure and Acyclovir Resistance

Suspect resistance if lesions do not begin to resolve within 7-10 days of therapy initiation. 2

Management approach:

• Obtain viral culture and susceptibility testing to confirm resistance 2
• IV foscarnet 40 mg/kg three times daily is the treatment of choice for acyclovir-resistant HSV 2, 3
• Topical trifluridine, cidofovir, or imiquimod can be used for lesions on external surfaces, requiring 21-28 days or longer of application 2
• Acyclovir-resistant strains are typically cross-resistant to ganciclovir 2

Pregnancy

Acyclovir is the first choice for HSV infections in pregnancy due to the most extensive safety data. 2

• Episodic therapy for first-episode and recurrent disease can be offered during pregnancy 2
• Suppressive therapy is not routinely used during pregnancy 2
• Visceral HSV disease is more likely and can be fatal during pregnancy 2
• Use of acyclovir in late pregnancy suppresses outbreaks and reduces the need for cesarean delivery 2

Renal Impairment

Dose adjustments are required based on creatinine clearance for all oral antivirals. 2, 3

• In patients aged ≥80 years, assess renal function before initiating therapy to avoid drug accumulation and neurotoxicity 3
• For high-dose IV acyclovir, monitor renal function at initiation and once or twice weekly during treatment 2
• Reduce dosing frequency based on creatinine clearance 3

Common Pitfalls to Avoid

Critical errors to prevent:

• Never rely on topical acyclovir alone—it is substantially less effective than systemic therapy 2, 1, 3, 5
• Do not delay treatment beyond 24 hours for recurrences—efficacy decreases significantly after this window 1, 3
• Do not use short-course (1-3 day) therapy in HIV-infected or immunocompromised patients 2
• Do not fail to discuss suppressive therapy with patients experiencing ≥6 recurrences per year 1, 3
• Do not forget to counsel patients that asymptomatic viral shedding can occur, and transmission is possible even without visible lesions 1, 3, 5

Adverse Effects and Monitoring

Common side effects (generally mild to moderate):

• Headache (affecting <10% of patients) 1, 3
• Nausea (<4%) 1, 3
• Diarrhea 1, 3

Monitoring requirements:

• No laboratory monitoring needed for episodic or suppressive therapy unless substantial renal impairment exists 2
• For high-dose IV acyclovir, monitor renal function regularly 2
• Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome has been reported with high-dose (8 g/day) valacyclovir in HIV-infected patients, but not at standard HSV treatment doses 2

Patient Counseling and Transmission Prevention

Essential counseling points:

• HSV-1 is a chronic, incurable infection with potential for lifelong recurrence 1
• Avoid direct contact (kissing, sharing utensils, towels, lip balm) when lesions or prodromal symptoms are present 1, 3
• Patients remain contagious until all lesions are fully crusted 3
• Even with optimal antiviral therapy, viral shedding persists for approximately 6.4 days (versus 8.1 days without treatment) 3
• Transmission can occur during asymptomatic periods, though less frequently with HSV-1 than HSV-2 1, 3, 5
• Identify and avoid personal triggers: UV light exposure, fever, psychological stress, menstruation 1, 3
• Apply sunscreen (SPF ≥15) or zinc oxide to prevent UV-triggered recurrences 1, 3