What is the recommended antiviral treatment regimen for an initial genital herpes outbreak and for recurrent episodes in an otherwise healthy adult?

Treatment of Herpes Outbreak

For an initial genital herpes outbreak in an otherwise healthy adult, start valacyclovir 1 g orally twice daily for 7–10 days; for recurrent episodes, initiate valacyclovir 500 mg orally twice daily for 5 days at the first sign of prodrome or within 24 hours of lesion onset. 1

Initial (First-Episode) Genital Herpes Treatment

Recommended oral antiviral regimens for first clinical episodes:

• Valacyclovir 1 g orally twice daily for 7–10 days (preferred for convenience) 1, 2
• 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

Extend treatment beyond 10 days if healing is incomplete at day 10. 1 For severe ulcerative disease with large lesions, continue therapy for at least 2 weeks to achieve complete clinical healing. 1

Severe Disease Requiring Hospitalization

For disseminated infection, encephalitis, pneumonitis, hepatitis, or inability to tolerate oral medication, administer acyclovir 5–10 mg/kg IV every 8 hours for 5–7 days or until clinical resolution. 1 This applies to patients with central nervous system involvement, visceral organ involvement, or extensive mucocutaneous disease preventing oral intake. 1

Special Anatomic Considerations

For first-episode herpes proctitis, use acyclovir 400 mg orally five times daily for 10 days (higher dosing and longer duration than standard genital herpes regimens due to rectal site requirements). 1

Recurrent Episode Treatment (Episodic Therapy)

Timing is critical: initiate treatment during prodrome or within 24 hours of lesion onset when viral replication peaks. 1 Provide patients with a prescription to self-initiate at the first sign of recurrence. 1, 2

Recommended 5-day episodic regimens:

• Valacyclovir 500 mg orally twice daily 1
• Acyclovir 800 mg orally twice daily 1
• Acyclovir 400 mg orally three times daily 1
• Famciclovir 125 mg orally twice daily 1

Valacyclovir and famciclovir offer more convenient dosing schedules with comparable efficacy to acyclovir. 2

Suppressive (Chronic) Therapy

Offer daily suppressive therapy to patients experiencing ≥6 recurrences per year, which reduces recurrence frequency by ≥75%. 3, 1

Dosing Based on Recurrence Frequency

For immunocompetent patients with <10 recurrences per year:

• Valacyclovir 500 mg orally once daily 3
• Acyclovir 400 mg orally twice daily (safety documented up to 6 years) 3, 1
• Famciclovir 250 mg orally twice daily (safety documented up to 1 year) 3, 1

For patients with ≥10 recurrences per year:

• Valacyclovir 1000 mg orally once daily (500 mg once daily is less effective in this population) 3, 1

For HIV-infected patients with CD4+ count ≥100 cells/mm³:

• Valacyclovir 500 mg orally twice daily (not once daily—twice-daily dosing is required for adequate viral control) 3, 1

Duration and Reassessment

After 1 year of continuous suppressive therapy, discontinue temporarily to reassess recurrence frequency, as outbreak rates often decline naturally over time. 3, 1 Safety and efficacy are documented for acyclovir up to 6 years and for valacyclovir/famciclovir up to 1 year. 1

Critical Pitfalls to Avoid

Do not use topical acyclovir as monotherapy—it is substantially less effective than systemic oral antivirals and does not improve systemic symptoms, viremia, or viral shedding from cervix, urethra, or pharynx. 1, 2

Do not delay episodic therapy beyond 24 hours of lesion onset—starting treatment during prodrome or within 1 day maximizes efficacy. 1

Do not use valacyclovir 500 mg once daily in patients with ≥10 recurrences per year—it is inadequate for this population. 3, 1

Do not use valacyclovir 500 mg once daily in HIV-infected patients—twice-daily dosing (500 mg BID) is required. 3, 1

Renal Function Considerations

Assess renal function before starting therapy and adjust dosing for creatinine clearance <30 mL/min (reduce to 500 mg every 24–48 hours); no adjustment needed for CrCl 30–49 mL/min. 3 Monitor renal function during therapy, especially in patients with baseline impairment. 1

Antiviral Resistance Management

Suspect acyclovir resistance if lesions fail to improve within 7–10 days of appropriate therapy. 3, 1 Obtain viral culture with susceptibility testing to confirm resistance. 1

For confirmed acyclovir-resistant HSV, administer IV foscarnet 40 mg/kg every 8 hours until clinical resolution (all acyclovir-resistant strains are also resistant to valacyclovir). 3, 1 Resistance is rare in immunocompetent patients (<0.5%) but more common in immunocompromised individuals (5–7%). 3

Pregnancy Considerations

For pregnant women with genital herpes, initiate antiviral prophylaxis from 36 weeks gestation until delivery to reduce term-time recurrences and cesarean delivery rates. 1 Acyclovir is preferred during pregnancy given the largest safety experience base. 3

Perform cesarean delivery if any of the following are present at labor onset:

• Suspected or confirmed first-episode genital herpes 1
• First episode occurring <6 weeks before delivery 1
• Prodrome or visible lesions at labor onset 1

Patient Counseling Essentials

Inform patients that genital herpes is a chronic, incurable infection with potential for lifelong recurrences. 1

Emphasize that asymptomatic viral shedding can occur even without visible lesions and even while on suppressive therapy, allowing transmission to partners. 3, 1

Advise patients to abstain from all sexual activity during active lesions or prodromal symptoms. 1

Recommend condom use for all sexual encounters with new or uninfected partners, although condoms do not completely eliminate transmission risk. 1

Explain that neonatal transmission risk is 25–44% with a primary episode at delivery versus ≈1% with recurrent infection. 1

Inform all sexual partners about the herpes diagnosis. 1