How do you treat genital herpes in a healthy adult, including first episode, recurrent disease, pregnancy, and renal impairment?

Treatment of Genital Herpes

For first-episode genital herpes, treat with valacyclovir 1 gram orally twice daily for 7-10 days, extending treatment if healing is incomplete at 10 days. 1

First Episode Treatment

Recommended regimens for initial genital herpes:

• Valacyclovir 1 gram orally twice daily for 7-10 days (preferred due to convenient dosing and equivalent efficacy to acyclovir) 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

Treatment duration must be extended beyond 10 days if lesions have not completely healed. 1 Topical acyclovir should never be used as it is substantially less effective than oral therapy and provides no improvement in systemic symptoms. 1, 3

Recurrent Episodes Treatment

Episodic Therapy

For recurrent outbreaks, initiate treatment during prodrome or within 1 day of lesion onset for maximum benefit:

• Valacyclovir 500 mg orally twice daily for 5 days 4
• Acyclovir 800 mg orally twice daily for 5 days 4
• Acyclovir 400 mg orally three times daily for 5 days 4
• Famciclovir 125 mg orally twice daily for 5 days 4

Patients should be provided with medication or a prescription in advance to initiate treatment immediately at first sign of prodrome or lesions. 4, 1

Suppressive Therapy

Daily suppressive therapy should be offered to patients with ≥6 recurrences per year, as it reduces recurrence frequency by ≥75%:

• Valacyclovir 1 gram orally once daily (most effective, especially for patients with ≥10 recurrences per year) 5
• Valacyclovir 500 mg orally once daily (appropriate for <10 recurrences per year, but less effective for very frequent recurrences) 4, 5
• Acyclovir 400 mg orally twice daily (documented safety up to 6 years) 4, 5
• Famciclovir 250 mg orally twice daily (documented safety up to 1 year) 4, 5

After 1 year of continuous suppressive therapy, discontinue treatment temporarily to reassess recurrence frequency, as recurrences naturally decrease over time in many patients. 4

Severe Disease Requiring Hospitalization

For severe disease with complications such as disseminated infection, pneumonitis, hepatitis, meningitis, or encephalitis:

• Acyclovir 5-10 mg/kg IV every 8 hours for 5-7 days or until clinical resolution 4

Treatment During Pregnancy

Acyclovir is the first-choice antiviral for HSV infections during pregnancy due to the most extensive safety data:

First Episode During Pregnancy

• Acyclovir 200 mg orally 5 times daily for 5-10 days 6
• Valacyclovir 1000 mg orally twice daily for 5-10 days 6

Recurrent Episodes During Pregnancy

• Acyclovir 200 mg orally 5 times daily 6
• Valacyclovir 500 mg orally twice daily 6

Suppressive Therapy in Late Pregnancy

Antiviral prophylaxis from 36 weeks gestation until delivery should be offered to women with either first or recurrent episodes during pregnancy to reduce recurrences at term and cesarean delivery rates. 6 This typically uses acyclovir or valacyclovir at suppressive doses. 4, 6

Cesarean delivery is recommended if:

• A first episode of genital herpes is suspected or confirmed at onset of labor 6
• A first episode occurred less than 6 weeks before delivery 6
• Genital herpes prodrome or visible lesions are present at onset of labor 4

The risk of neonatal transmission is 25-44% with primary first episode at delivery versus only 1% with recurrent herpes. 6

Renal Impairment Dosing

All antiviral medications require dose adjustment for renal impairment to prevent acute renal failure and toxicity. While specific adjustments vary by creatinine clearance and medication, general principles include:

• Monitor renal function before initiating therapy and during treatment 4
• Reduce dosing frequency and/or total daily dose based on creatinine clearance 4
• Avoid high-dose valacyclovir (8 grams per day) in any patient with renal compromise due to risk of hemolytic uremic syndrome/thrombotic thrombocytopenic purpura 5

HIV-Infected Patients

For HIV-infected patients, higher or more frequent dosing may be required:

Suppressive Therapy

• Valacyclovir 500 mg orally twice daily (not once daily, as twice-daily dosing is necessary in HIV patients) 4, 5
• Famciclovir 500 mg orally twice daily has demonstrated effectiveness in decreasing recurrence rates and subclinical shedding 5

Daily suppressive therapy in HIV-infected persons reduces HIV concentration in plasma and genital secretions, though clinical benefit regarding HIV transmission remains uncertain. 4

Treatment Failure and Acyclovir Resistance

Suspect acyclovir resistance if lesions do not begin to resolve within 7-10 days of appropriate therapy. 4, 5

For confirmed or suspected acyclovir-resistant HSV:

• Obtain viral culture and susceptibility testing 4
• IV foscarnet 40 mg/kg every 8 hours is the treatment of choice 4, 5
• Topical cidofovir, trifluridine, or imiquimod may be used for external lesions, requiring prolonged application for 21-28 days or longer 4

Resistance is rare in immunocompetent patients but more common in immunocompromised individuals, particularly those with HIV receiving prolonged suppressive therapy. 4, 3

Critical Patient Counseling Requirements

All patients must be counseled about:

• The natural history of genital herpes, including potential for recurrent episodes and lifelong infection 1
• Asymptomatic viral shedding can occur even on suppressive therapy, potentially leading to transmission 5, 1
• Abstain from sexual activity when lesions or prodromal symptoms are present 5, 1
• Inform all sex partners about having genital herpes 5, 1
• Use condoms during all sexual exposures with new or uninfected partners 5, 1
• Antiviral medications control symptoms but do not eradicate the virus or prevent all recurrences 5, 1
• The risk of neonatal infection, especially for childbearing-aged women who should inform prenatal care providers 4, 1
• HSV-2 causes more frequent asymptomatic shedding than HSV-1, particularly in the first 12 months after infection 4, 1

Common Pitfalls to Avoid

• Never use topical acyclovir - it is substantially less effective than oral therapy 5, 1
• Do not use valacyclovir 500 mg once daily for patients with ≥10 recurrences per year - it is less effective than other regimens 4, 5
• Do not stop treatment at exactly 7-10 days for first episodes if lesions have not completely healed - extend treatment until complete healing 1
• Do not delay treatment for recurrent episodes - efficacy is maximized when started during prodrome or within 1 day of lesion onset 4, 1
• Do not forget dose adjustments for renal impairment - failure to adjust can cause acute renal failure 5