What is the recommended treatment for an immunocompetent adult patient presenting with Herpes Simplex Virus 1 (HSV-1)?

Treatment of Herpes Simplex Virus 1 (HSV-1) in Immunocompetent Adults

For immunocompetent adults with HSV-1 infection, oral antiviral therapy with valacyclovir, famciclovir, or acyclovir is the recommended treatment, with the specific regimen depending on the anatomic site and whether this is a first episode or recurrent disease. 1, 2, 3, 4

Orolabial HSV-1 (Cold Sores)

First Episode or Severe Disease

• Valacyclovir 2 grams orally twice daily for 1 day is the preferred first-line treatment when initiated at earliest symptoms (prodrome or within 24 hours of lesion onset) 2, 3
• Alternative: Famciclovir 1500 mg orally as a single dose 2, 4
• Alternative: Acyclovir 400 mg orally five times daily for 5 days (requires more frequent dosing) 2

Critical timing consideration: Treatment must be initiated during the prodromal phase or within 24 hours of symptom onset for maximum efficacy, as peak viral titers occur in the first 24 hours after lesion onset 2

Recurrent Episodes (≥6 per year)

For patients with frequent recurrences, daily suppressive therapy reduces recurrence frequency by ≥75% 2:

• Valacyclovir 500 mg orally once daily (can increase to 1000 mg once daily for very frequent recurrences) 2
• Alternative: Famciclovir 250 mg orally twice daily 2
• Alternative: Acyclovir 400 mg orally twice daily 2

Safety and efficacy documented for acyclovir up to 6 years and valacyclovir/famciclovir for 1 year 2. After 1 year of continuous suppressive therapy, consider discontinuation to reassess recurrence frequency 2.

Severe Intraoral HSV-1 (Gingivostomatitis)

• Mild cases: Acyclovir 20 mg/kg (maximum 400 mg/dose) orally three times daily for 5-10 days 2
• Moderate to severe cases requiring hospitalization: Acyclovir 5-10 mg/kg IV every 8 hours until lesions begin to regress, then switch to oral therapy and continue until complete healing 2

Genital HSV-1

First Clinical Episode

Treatment should be initiated within 72 hours of symptom onset 1, 3:

• Valacyclovir 1 gram orally twice daily for 7-10 days 1, 3
• Alternative: Acyclovir 400 mg orally three times daily for 7-10 days 1
• Alternative: Acyclovir 200 mg orally five times daily for 7-10 days 1
• Alternative: Famciclovir 250 mg orally three times daily for 7-10 days 1, 4

Treatment may be extended if healing is incomplete after 10 days 1.

Important prognostic information: HSV-1 causes 5-30% of first-episode genital herpes cases, but clinical recurrences are much less frequent for genital HSV-1 than HSV-2 infection 1. This should be communicated to patients for counseling purposes.

Recurrent Episodes

Episodic therapy is most effective when started during prodrome or within 1 day after onset of lesions 1, 5:

• Valacyclovir 500 mg orally twice daily for 5 days 1, 5, 3
• Alternative: Acyclovir 400 mg orally three times daily for 5 days 1, 5
• Alternative: Acyclovir 800 mg orally twice daily for 5 days 1, 5
• Alternative: Acyclovir 200 mg orally five times daily for 5 days 1, 5
• Alternative: Famciclovir 125 mg orally twice daily for 5 days 1, 5, 4

Suppressive Therapy (for ≥6 recurrences per year)

Daily suppressive therapy reduces recurrence frequency by ≥75% 1, 5:

• Acyclovir 400 mg orally twice daily 1, 5
• Alternative: Valacyclovir 1000 mg orally once daily 1, 3
• Alternative: Valacyclovir 500 mg orally once daily 1, 3
• Alternative: Famciclovir 250 mg orally twice daily 1, 4

Note: Valacyclovir 500 mg once daily appears less effective in patients with very frequent recurrences (≥10 episodes per year) 1. Safety documented for acyclovir up to 6 years and valacyclovir/famciclovir for 1 year 1, 3, 4. After 1 year, discontinue to reassess recurrence rate 1, 5.

Severe or Disseminated HSV-1 Disease

For severe disease requiring hospitalization (disseminated infection, pneumonitis, hepatitis, CNS complications such as meningitis or encephalitis) 1:

• Acyclovir 5-10 mg/kg IV every 8 hours for 5-7 days or until clinical resolution 1
• Monitor renal function at initiation and once or twice weekly during treatment 1

Treatment Failure and Acyclovir Resistance

Suspect acyclovir resistance if lesions do not begin to resolve within 7-10 days of therapy 1, 2:

• Obtain viral culture and susceptibility testing if virus is isolated 1
• For confirmed acyclovir-resistant HSV: Foscarnet 40 mg/kg IV every 8 hours is the treatment of choice 1, 2, 6

Resistance rates: <0.5% in immunocompetent patients, but up to 7% in immunocompromised patients 2, 6

Critical Counseling Points

For All HSV-1 Patients

• HSV-1 is a recurrent, incurable viral disease; antiviral medications control symptoms but do not eradicate latent virus 1, 5, 7
• Abstain from sexual activity (for genital herpes) or close contact (for orolabial herpes) when lesions or prodromal symptoms are present 1, 5
• Asymptomatic viral shedding can occur, potentially leading to transmission even without visible lesions 1, 5
• Suppressive therapy reduces but does not eliminate asymptomatic viral shedding 1, 2

Trigger Avoidance

Patients should identify and avoid personal triggers including ultraviolet light exposure, fever, psychological stress, and menstruation 2

Common Pitfalls to Avoid

• Do not use topical acyclovir: It is substantially less effective than oral therapy and its use is discouraged 1, 2, 5
• Do not delay treatment: Efficacy decreases significantly when treatment is initiated after lesions have fully developed 2
• Do not use short-course therapy designed for genital herpes for herpes zoster: These regimens are inadequate for VZV infection 8
• Do not fail to consider suppressive therapy in patients with ≥6 recurrences per year who could significantly benefit 2
• Do not use valacyclovir 8 grams per day: This dose is associated with hemolytic uremic syndrome/thrombotic thrombocytopenic purpura in immunocompromised patients 5

Renal Dosing Adjustments

Dose adjustments are mandatory for patients with renal impairment to prevent acute renal failure 2. Specific adjustments should be made based on creatinine clearance for acyclovir, valacyclovir, and famciclovir 2, 3, 4.