What is the recommended treatment for Herpes Simplex Virus type 2 (HSV-2) on the penis?

Treatment of HSV-2 Genital Infection on the Penis

For recurrent HSV-2 on the penis, treat with valacyclovir 500 mg orally twice daily for 5 days, initiated at the first sign of prodrome or lesion onset. 1

Treatment Approach Based on Episode Type

For Recurrent Episodes (Most Common Scenario)

Episodic therapy is the standard approach for recurrent genital HSV-2 outbreaks:

• Valacyclovir 500 mg orally twice daily for 5 days is the CDC-recommended first-line regimen 1
• Alternative options include acyclovir 400 mg orally three times daily for 5 days, acyclovir 800 mg orally twice daily for 5 days, or famciclovir 125 mg orally twice daily for 5 days 1
• Treatment must be started during prodrome or within 1 day of lesion onset for maximum effectiveness 1
• Median time to lesion healing with valacyclovir 500 mg is 4 days versus 6 days with placebo 2
• Median time to cessation of viral shedding is 2 days with valacyclovir versus 4 days with placebo 2

For First Clinical Episode

If this is the initial HSV-2 outbreak on the penis, longer treatment duration is required:

• Valacyclovir 1 g orally twice daily for 7-10 days 3
• Alternative regimens: acyclovir 400 mg orally three times daily for 7-10 days, or famciclovir 250 mg orally three times daily for 7-10 days 3
• Treatment may be extended beyond 10 days if healing is incomplete 3

For Frequent Recurrences (≥6 Episodes Per Year)

Daily suppressive therapy should be offered:

• Valacyclovir 1 g orally once daily or valacyclovir 500 mg orally once daily 1
• Alternative options: acyclovir 400 mg orally twice daily or famciclovir 250 mg orally twice daily 1
• Suppressive therapy reduces recurrence frequency by ≥75% 1
• After 1 year of continuous suppressive therapy, consider discontinuation to reassess recurrence frequency 1

Critical Treatment Considerations

What NOT to Do

• Never use topical acyclovir—it is substantially less effective than oral therapy 1, 3
• Avoid valacyclovir 8 grams per day in immunocompromised patients due to risk of hemolytic uremic syndrome/thrombotic thrombocytopenic purpura 1

When to Suspect Treatment Failure

• If lesions do not begin to resolve within 7-10 days of therapy, suspect acyclovir resistance 1
• For proven or suspected resistance, use foscarnet 40 mg/kg IV every 8 hours 1

For Severe Disease Requiring Hospitalization

• Acyclovir 5-10 mg/kg IV every 8 hours for 5-7 days or until clinical resolution 3

Essential Patient Counseling

Patients must understand the following:

• Genital herpes is a recurrent, incurable viral disease; antiviral medications control symptoms but do not eradicate the virus 1
• Abstain from sexual activity when lesions or prodromal symptoms are present 1
• Asymptomatic viral shedding can occur, potentially leading to transmission even without visible lesions 1
• Inform all sex partners about having genital herpes 1
• Use condoms during all sexual exposures with new or uninfected partners 1

Transmission Reduction Strategy

For patients concerned about transmitting HSV-2 to partners:

• Daily valacyclovir 500 mg reduces HSV-2 transmission risk by 48% and reduces clinical disease in susceptible partners by 75% 2, 4
• This should be combined with safer sex practices including consistent condom use 4

Comparative Efficacy Note

While both famciclovir and valacyclovir are effective, valacyclovir appears somewhat superior for suppression of genital herpes and associated viral shedding compared to famciclovir 5. Valacyclovir detected HSV on 1.3% of days versus 3.2% with famciclovir during suppressive therapy 5.