What is the recommended treatment for genital herpes in a healthy adult, including management of primary outbreak, recurrent episodes, and suppressive therapy?

Treatment for Genital Herpes

For genital herpes in healthy adults, use oral antiviral therapy with valacyclovir, acyclovir, or famciclovir, tailored to whether the patient presents with a first episode, recurrent outbreak, or requires suppressive therapy for frequent recurrences (≥6 per year). 1

First Clinical Episode (Primary Outbreak)

Initiate oral antiviral therapy for 7–10 days using one of the following CDC-recommended regimens 1:

• Valacyclovir 1 g orally twice daily (preferred for convenience) 1, 2
• Acyclovir 400 mg orally three times daily 1
• Acyclovir 200 mg orally five times daily 1
• Famciclovir 250 mg orally three times daily 1

Extend treatment beyond 10 days if healing is incomplete, particularly when ulcers are large or severe—continue for at least 2 weeks until complete clinical resolution. 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

Critical Pitfall to Avoid

Never use topical acyclovir as monotherapy—it is substantially less effective than oral therapy and does not reduce systemic symptoms, viremia, or viral shedding from the cervix, urethra, or pharynx. 1, 2, 3

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Recurrent Episodes (Episodic Therapy)

Start treatment during the prodrome or within 1 day of lesion onset to maximize efficacy, as peak viral replication occurs in the first 24 hours. 1, 2

Provide patients with a prescription to self-initiate at the first sign of recurrence. 1, 2

CDC-Recommended 5-Day Episodic Regimens 1, 3:

• Valacyclovir 500 mg orally twice daily (preferred for convenience) 1
• Acyclovir 800 mg orally twice daily 1
• Acyclovir 400 mg orally three times daily 1
• Famciclovir 125 mg orally twice daily 1

Valacyclovir is FDA-approved for a 3-day episodic regimen, though the 5-day course is more commonly recommended in guidelines. 4

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Suppressive Therapy (Chronic Daily Treatment)

Offer daily suppressive therapy to patients with ≥6 recurrences per year, which reduces recurrence frequency by ≥75%. 1, 2, 3

CDC-Recommended Suppressive Regimens 1:

• Valacyclovir 1 g orally once daily (standard dose) 1
• Valacyclovir 500 mg orally once daily (for patients with <10 recurrences per year) 1
• Acyclovir 400 mg orally twice daily (safety documented up to 6 years) 1, 5
• Famciclovir 250 mg orally twice daily (safety documented up to 1 year) 1

Valacyclovir is the only antiviral FDA-approved for once-daily suppressive therapy, improving adherence. 4, 6

When to Reassess

After 1 year of continuous suppressive therapy, discontinue temporarily to reassess recurrence frequency, as the natural history often shows declining recurrence rates over time. 1, 2

Patient Preference Data

Suppressive therapy is strongly preferred by patients over episodic treatment (72% preference), with significantly greater treatment satisfaction and quality of life. 7

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Special Populations & Considerations

Pregnancy

Administer antiviral prophylaxis from 36 weeks gestation until delivery to reduce term recurrences and cesarean delivery rates. 1

Perform cesarean delivery if any of the following are present at labor onset 1:

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

The neonatal transmission risk is 25–44% with primary infection at delivery versus ≈1% with recurrent infection. 1

HIV-Infected Patients

Use valacyclovir 500 mg orally twice daily (not once daily) for suppressive therapy to achieve adequate viral control. 1

Daily suppressive therapy reduces HIV RNA concentrations in plasma and genital secretions. 1

Immunocompromised Patients

Higher doses are required: acyclovir 400 mg orally three to five times daily until clinical resolution. 1

Suspect acyclovir resistance if lesions fail to improve within 7–10 days—confirm with viral culture and susceptibility testing, then switch to IV foscarnet 40 mg/kg every 8 hours. 1, 3

Resistance is uncommon in immunocompetent hosts but more frequent in immunocompromised patients on long-term suppressive therapy. 1

Renal Function

Assess renal function before starting and during therapy—adjust dosing frequency or total daily dose according to creatinine clearance to avoid toxicity. 1

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Essential Patient Counseling

Inform patients that genital herpes is a chronic, incurable infection with potential for lifelong recurrences; antivirals control symptoms but do not eradicate the virus. 1, 2, 3

Asymptomatic viral shedding can occur even on suppressive therapy, posing transmission risk—HSV-2 sheds more frequently than HSV-1, especially in the first 12 months after infection. 1, 2

Patients must abstain from sexual activity when lesions or prodromal symptoms are present and should inform all sexual partners about their HSV status. 1, 2, 3

Condoms should be used during all sexual encounters with new or uninfected partners, though they do not completely eliminate transmission risk. 1, 2, 3

Women of childbearing age must understand neonatal infection risk and inform healthcare providers about HSV infection if pregnant. 1, 2

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HSV-1 vs. HSV-2 Prognostic Differences

HSV-1 causes 5–30% of first-episode genital herpes cases but has much less frequent clinical recurrences than HSV-2. 1

Identification of the infecting strain (HSV-1 vs. HSV-2) has prognostic importance and is useful for counseling about recurrence frequency and transmission risk. 1, 2