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

Treatment of HSV-1 Infection in Immunocompetent Adults

For an immunocompetent adult with uncomplicated HSV-1 infection, initiate oral antiviral therapy with valacyclovir 1 gram twice daily for 7-10 days, which offers superior bioavailability and convenience compared to acyclovir. 1

First-Line Oral Antiviral Options

The CDC establishes three equally effective first-line regimens for first-episode HSV-1 infection 1:

• Valacyclovir 1 gram orally twice daily for 7-10 days (preferred due to convenient dosing) 1
• Acyclovir 400 mg orally three times daily for 7-10 days 1
• Acyclovir 200 mg orally five times daily for 7-10 days 1
• Famciclovir 250 mg orally three times daily for 7-10 days 1

Valacyclovir and famciclovir are preferred over standard-dose acyclovir due to better bioavailability and less frequent dosing, which improves adherence. 2

Treatment Duration and Monitoring

• Continue treatment for 7-10 days, extending beyond 10 days if healing remains incomplete 1
• The key clinical endpoint is complete healing of lesions, not an arbitrary calendar duration 1
• For severe oral manifestations (stomatitis, pharyngitis), higher acyclovir doses (400 mg five times daily) have been used historically, though optimal dosing remains uncertain 1

Critical Management Principles

Systemic oral therapy is essential—topical acyclovir is substantially less effective than oral therapy and should be avoided. 1, 2

When to Escalate to IV Therapy

Intravenous acyclovir is reserved for 2:

• Severe disease requiring hospitalization 1
• Inability to tolerate oral medications 1
• Disseminated HSV infection 1
• Immunocompromised patients with severe presentations 3

Common Pitfalls to Avoid

• Do not use topical antivirals as monotherapy—they are inadequate for systemic HSV control 1, 2
• Do not apply topical corticosteroids—these potentiate HSV infection and risk dissemination 2
• Do not delay treatment waiting for laboratory confirmation—initiate therapy immediately based on clinical presentation 2

Recurrent HSV-1 Management

For recurrent episodes in immunocompetent patients 4, 5:

• Mild disease: Consider topical acyclovir 5% cream or penciclovir 1% cream (though less effective than oral therapy) 4
• Moderate-to-severe recurrences: Episodic oral therapy with same regimens as primary infection 5
• Frequent recurrences (>5 episodes/year): Consider chronic suppressive therapy with acyclovir 400 mg twice daily 5

Resistance Considerations

Acyclovir resistance is rare in immunocompetent patients 3, 6:

• If lesions fail to respond after 5-7 days of standard therapy, increase acyclovir to 800 mg five times daily 3
• If no response after dose escalation, consider alternative diagnosis or obtain viral culture with susceptibility testing 3
• For confirmed resistance (extremely rare in immunocompetent hosts): foscarnet 40 mg/kg IV three times daily or topical trifluridine 3, 6

Patient Counseling

Essential counseling points include 1:

• HSV-1 establishes lifelong latency with potential for recurrent episodes 1
• Asymptomatic viral shedding can occur, allowing transmission even without visible lesions 1
• Abstain from intimate contact when lesions or prodromal symptoms are present 1
• Use barrier protection with new or uninfected partners 1