What is the recommended treatment for penile herpes in an adult male (first episode and recurrent outbreaks)?

Treatment of Penile Herpes

For first-episode genital herpes, oral acyclovir 400 mg three times daily for 7-10 days is the recommended treatment, while recurrent episodes should be treated with acyclovir 800 mg twice daily for 5 days when initiated during prodrome or within 1-2 days of lesion onset. 1, 2

First Clinical Episode (Primary Infection)

Recommended Treatment Regimens

Oral systemic therapy is mandatory—topical acyclovir is substantially less effective and should never be used for genital herpes. 1, 2

First-line options for initial episodes include:

• Acyclovir 400 mg orally three times daily for 7-10 days 2
• Acyclovir 200 mg orally 5 times daily for 7-10 days 1
• Valacyclovir 1 gram orally twice daily for 7-10 days 2, 3
• Famciclovir 250 mg orally three times daily for 7-10 days 2

Clinical Characteristics to Expect

First-episode infections present with more extensive disease than recurrences, including 4:

• Severe genital lesions with painful vesicles on the penis, glans, or prepuce 5, 4
• Systemic symptoms (fever, malaise, lymphadenopathy) in many patients 5, 4
• Greater viral shedding compared to recurrent episodes 4
• Possible urethral involvement (virus isolated from urethra in ~30% of males) 4

Treatment should continue for the full 7-10 days or until complete clinical resolution is achieved. 1

Recurrent Episodes

Treatment Approach

Most immunocompetent patients with recurrent disease experience limited benefit from therapy unless treatment is initiated during prodrome or within 1-2 days of lesion onset. 1, 6

Recommended regimens for recurrent episodes (5-day courses):

• Acyclovir 800 mg orally twice daily for 5 days (preferred for convenience) 1, 2
• Acyclovir 400 mg orally three times daily for 5 days 1, 2
• Acyclovir 200 mg orally five times daily for 5 days 1, 6
• Valacyclovir 500 mg orally twice daily for 5 days 2, 3

Timing Is Critical

Treatment must be self-initiated at the earliest sign of prodromal symptoms (tingling, burning) or within 24 hours of lesion appearance for maximum benefit. 2, 3 Starting therapy after this window significantly reduces effectiveness. 6

Clinical Outcomes

Recurrent episodes are much milder than primary infections, with 4:

• Less extensive disease
• Minimal or no systemic symptoms
• Shorter duration of viral shedding
• HSV-2 genital infections recur in approximately 95% of patients, while HSV-1 genital infections recur in only 50% 4

Suppressive Therapy (For Frequent Recurrences)

Indications

Daily suppressive therapy should be considered for patients with 6 or more recurrences per year, as it reduces recurrence frequency by at least 75%. 1

Recommended suppressive regimens:

• Valacyclovir 1 gram orally once daily 2, 3
• Acyclovir 400 mg orally twice daily 1, 2
• Valacyclovir 500 mg once daily (for patients with ≤9 recurrences/year) 3

Important Limitations

Suppressive therapy does not eliminate asymptomatic viral shedding or completely prevent transmission to sexual partners. 1 Acyclovir neither eradicates latent virus nor affects subsequent risk, frequency, or severity of recurrences after discontinuation. 1, 6

Critical Pitfalls to Avoid

Never Use Topical Therapy

Topical acyclovir is substantially less effective than oral systemic drugs and its use is strongly discouraged for genital herpes. 1, 2 Topical therapy fails to achieve adequate therapeutic levels and will result in inadequate treatment with prolonged symptoms. 2

Never Use Topical Corticosteroids

Topical or systemic corticosteroids are absolutely contraindicated in HSV infections, as they potentiate viral replication and worsen disease. 2

Counsel Patients on Transmission

• Avoid sexual contact during active outbreaks 5
• Use condoms to reduce (but not eliminate) transmission risk 5
• Asymptomatic viral shedding occurs and can transmit infection even without visible lesions 1, 4
• Suppressive antiviral therapy in the infected partner reduces transmission to serodiscordant partners 5

Special Considerations

Severe or Complicated Disease

For extensive first-episode disease requiring hospitalization, or for immunocompromised patients with severe manifestations, intravenous acyclovir may be necessary. 1 Acyclovir 400 mg orally 5 times daily for 10 days is recommended for first-episode herpes proctitis. 1

HIV-Infected Patients

HIV-infected patients may require more aggressive therapy with higher doses or longer treatment courses, as they can experience prolonged episodes with extensive disease. 1 Acyclovir-resistant strains may develop in immunocompromised patients receiving prolonged suppressive therapy, requiring alternative antiviral agents. 1