What is the recommended treatment for a patient with a history of recurrent Herpes Simplex Virus (HSV) outbreaks?

HSV Suppressive Therapy

For patients with recurrent HSV outbreaks, daily suppressive therapy with valacyclovir 500 mg once daily or 1 gram once daily is the preferred treatment approach for those experiencing ≥6 recurrences per year, reducing outbreak frequency by ≥75%. 1, 2

Treatment Strategy Selection

Indications for Daily Suppressive Therapy

• Patients with ≥6 recurrences per year should be offered daily suppressive therapy as the primary management strategy 1, 2
• Suppressive therapy reduces recurrence frequency by at least 75% in patients with frequent outbreaks 3, 1
• Daily suppressive therapy decreases asymptomatic viral shedding, which reduces transmission risk to sexual partners 1
• Long-term safety has been documented for up to 6 years with acyclovir and 1 year with valacyclovir 3, 1

When Episodic Therapy Is Appropriate

• Patients with <6 recurrences per year should receive episodic treatment rather than continuous suppression 1, 4
• Episodic therapy is suitable for patients who can reliably recognize prodromal symptoms and self-initiate treatment 4
• Most immunocompetent patients with infrequent recurrent disease do not benefit from continuous antiviral therapy 1

Recommended Suppressive Regimens

First-Line Options

• Valacyclovir 500 mg orally once daily (preferred for convenience of once-daily dosing) 1, 5
• Valacyclovir 1 gram orally once daily 3, 5
• Acyclovir 400 mg orally twice daily 3
• Famciclovir 250 mg orally twice daily 3

Special Dosing Considerations

• Valacyclovir 500 mg once daily appears less effective in patients with very frequent recurrences (≥10 episodes per year); use higher doses for these patients 3
• In HIV-infected patients with CD4+ count ≥100 cells/mm³, use valacyclovir 500 mg twice daily 5
• For patients with history of 9 or fewer recurrences per year, valacyclovir 500 mg once daily is appropriate 5

Episodic Treatment Regimens

Recommended Options for Acute Recurrences

• Valacyclovir 500 mg orally twice daily for 3-5 days (most convenient option) 2, 4, 5
• Acyclovir 400 mg orally three times daily for 5 days 3, 4
• Acyclovir 800 mg orally twice daily for 5 days 3, 4
• Acyclovir 200 mg orally five times daily for 5 days 3, 4
• Famciclovir 125 mg orally twice daily for 5 days 3, 4

Critical Timing for Episodic Treatment

• Treatment must be initiated during the prodrome or within 1 day (24 hours) of lesion onset to achieve maximum benefit 3, 1, 4
• Delaying treatment beyond 72 hours significantly reduces effectiveness 1, 4
• All patients should be provided with a prescription to self-initiate treatment at the first sign of recurrence, even if not on suppressive therapy 1, 4

Reassessment and Long-Term Management

Annual Evaluation

• After 1 year of continuous suppressive therapy, discontinue treatment to reassess the patient's recurrence frequency 3, 1, 2
• The frequency of recurrences decreases over time in many patients, making ongoing suppression potentially unnecessary 3
• Reassessment should include evaluation of the patient's psychological adjustment to genital herpes 3, 2

Switching Between Strategies

• Switch from episodic to suppressive therapy if recurrence frequency increases to ≥6 episodes per year 4
• Suppressive therapy has not been associated with emergence of clinically significant acyclovir resistance in immunocompetent patients 3

Essential Patient Counseling

Disease Education

• Inform patients about the chronic, recurrent nature of HSV infection and that antiviral medications control symptoms but do not eradicate the virus 1, 2, 4
• Explain that asymptomatic viral shedding can occur even without visible lesions, allowing transmission during symptom-free periods 3, 1, 2
• Discuss the potential for recurrent episodes and emphasize that recurrence frequency often decreases over time 3, 1

Transmission Prevention

• Advise patients to abstain from sexual activity when lesions or prodromal symptoms are present 3, 2, 4
• Encourage condom use during all sexual exposures with new or uninfected partners 3, 1, 4
• Inform all sex partners about the HSV diagnosis 3, 2
• Explain that suppressive therapy reduces but does not eliminate asymptomatic viral shedding 3

Pregnancy Considerations

• Women of childbearing age must inform prenatal care providers about their genital herpes history due to risk of neonatal infection 3, 1, 4
• Men should also be counseled about neonatal infection risk 3, 1

Critical Pitfalls to Avoid

Treatment Errors

• Never use topical acyclovir alone, as it is substantially less effective than systemic oral therapy 1, 2, 4
• Do not initiate suppressive therapy in patients with infrequent recurrences (<6 per year), as the benefit does not justify continuous medication 1, 2
• Do not withhold a prescription for episodic treatment from patients not on suppressive therapy; early self-initiated treatment is crucial 1

Dosing Cautions

• Avoid valacyclovir 8 grams per day in immunocompromised patients, as it is associated with hemolytic uremic syndrome/thrombotic thrombocytopenic purpura 2
• Do not delay prescribing episodic medication until an outbreak occurs; provide the prescription in advance 4

Resistance Considerations

• Suspect acyclovir resistance if lesions do not begin to resolve within 7-10 days of therapy 2
• For proven or suspected resistance, use foscarnet 40 mg/kg IV every 8 hours as an alternative 2