What is the recommended treatment for herpes simplex virus (HSV) infections?

Treatment of Herpes Simplex Virus (HSV) Infections

For acute HSV infections, initiate oral valacyclovir 1 g twice daily for 7-10 days for first episodes, or valacyclovir 500 mg twice daily for 5 days for recurrent episodes, starting treatment within 24 hours of lesion onset for maximum effectiveness. 1, 2

Treatment Algorithm by Clinical Scenario

First Episode (Primary Infection)

Preferred regimens for initial HSV-1 or HSV-2 infection:

• Valacyclovir 1 g orally twice daily for 7-10 days (first-line due to convenient dosing) 1, 2, 3
• Acyclovir 400 mg orally three times daily for 7-10 days (effective alternative, less expensive) 1, 2, 3
• Famciclovir 250 mg orally three times daily for 7-10 days 2, 3

Extend treatment beyond 10 days if healing is incomplete. 2, 3

For severe mucocutaneous disease requiring hospitalization, use IV acyclovir until lesions begin to regress, then transition to oral therapy. 3, 4

Recurrent Episodes (Episodic Therapy)

Critical timing: Treatment must be initiated during the prodrome or within 24 hours of lesion onset—peak viral replication occurs in the first 24 hours, and delayed treatment beyond 72 hours significantly reduces effectiveness. 1, 2

Preferred regimens for recurrent HSV-1 or HSV-2:

• Valacyclovir 500 mg orally twice daily for 5 days (most convenient) 1, 2
• Acyclovir 400 mg orally three times daily for 5 days 1, 2
• Famciclovir 125 mg orally twice daily for 5 days 1, 2

Provide patients with a prescription to self-initiate at first sign of recurrence—this is essential for effective treatment. 1

Suppressive Therapy (Chronic Daily Treatment)

Indications: Consider daily suppressive therapy for patients with ≥6 recurrences per year. 1, 2, 3

Benefits: Reduces recurrence frequency by ≥75% and decreases asymptomatic viral shedding, which may reduce transmission risk. 2, 3

Preferred regimens:

• Valacyclovir 500 mg orally once daily (for infrequent recurrences) 3
• Valacyclovir 1 g orally once daily (for frequent recurrences ≥10 episodes/year) 3
• Acyclovir 400 mg orally twice daily 2, 3
• Famciclovir 250 mg orally twice daily 2

After 1 year of continuous suppressive therapy, discontinue to reassess the patient's natural recurrence rate. 3

Special Populations

HIV-Infected Patients

HIV-infected patients require higher doses and longer treatment duration. 3

For suppressive therapy in HIV-infected patients:

• Valacyclovir 500 mg orally twice daily (not once daily) 3
• Acyclovir 400 mg orally twice daily 5

Do not use short-course therapy (1-3 days) in HIV-infected patients—it is ineffective. 2, 3

Pregnant Women

Acyclovir is the first-choice antiviral for HSV infections in pregnancy based on decades of safety data showing no pattern of adverse pregnancy outcomes. 5, 3

For episodic treatment during pregnancy: Use the same regimens as non-pregnant patients (acyclovir 400 mg three times daily for 7-10 days for first episodes, or 5 days for recurrences). 3

For suppressive therapy in pregnancy:

• Not routinely recommended unless the patient has frequent, severe recurrences 5, 3
• Consider starting at 36 weeks gestation for women with a history of genital herpes to reduce HSV shedding at delivery and decrease the need for cesarean delivery 3

Cesarean delivery is recommended for women with visible genital lesions or prodromal symptoms at the onset of labor, regardless of prior suppressive therapy. 3

Immunocompromised Patients (Non-HIV)

For severe mucocutaneous HSV lesions: IV acyclovir is first-line therapy until lesions begin to regress, then transition to oral therapy. 3, 4

Immunocompromised patients may require longer courses of therapy than immunocompetent patients. 2

Acyclovir-Resistant HSV

Suspect resistance if lesions do not begin to resolve within 7-10 days after initiating therapy. 2, 3

Diagnostic approach: Obtain viral culture of the lesion and perform susceptibility testing to confirm drug resistance. 2, 3

Treatment for confirmed acyclovir-resistant HSV:

• IV foscarnet 40 mg/kg every 8 hours (treatment of choice) 5, 2, 3, 6
• Alternative: IV cidofovir (for foscarnet failures) 5, 6

Note: Acyclovir-resistant HSV is routinely resistant to ganciclovir as well. 5

Critical Pitfalls to Avoid

Do not use topical acyclovir alone—it is substantially less effective than systemic therapy and is not recommended. 2, 3

Do not delay treatment beyond 72 hours for recurrences—effectiveness is significantly reduced. 1, 2

Do not assume treatment prevents all transmission—suppressive therapy reduces but does not eliminate transmission risk. Asymptomatic viral shedding still occurs. 2, 3

Adjust doses in patients with renal impairment to prevent toxicity, particularly in geriatric patients. 4

Monitoring Requirements

No laboratory monitoring is needed for patients on episodic or suppressive therapy unless substantial renal impairment exists. 2, 3

For patients receiving high-dose IV acyclovir: Monitor renal function at treatment initiation and once or twice weekly during treatment. 2, 4

Transmission Prevention Counseling

Patients must abstain from sexual activity when lesions or prodromal symptoms are present. 2, 3

Consistent condom use during all sexual exposures reduces transmission risk by approximately 50%. 2, 3

Counsel patients that asymptomatic viral shedding occurs (less frequently with HSV-1 than HSV-2), and transmission can occur even without visible lesions. 1, 3

Partners should be tested using type-specific serology and counseled about transmission risks. 3