What is the recommended management for genital herpes simplex virus (HSV) infections?

Management of Genital Herpes Simplex Virus (HSV) Infections

The recommended management for genital herpes includes both episodic and suppressive antiviral therapy with valacyclovir, acyclovir, or famciclovir, tailored to whether it's a first clinical episode or recurrent infection, with the dual goals of symptom relief and prevention of transmission. 1, 2

Diagnosis

• Accurate diagnosis should be established using type-specific molecular or virologic tests when genital ulcers are present, and type-specific serologic tests when lesions are not present 1
• Persons with genital symptoms consistent with herpes should undergo HSV-2 serologic testing to establish diagnosis 1
• Screening is not recommended for asymptomatic individuals with low pretest probability of infection or pregnant women 1
• Identifying the infecting strain (HSV-1 vs HSV-2) has prognostic importance, as HSV-1 causes 5-30% of first-episode genital herpes with less frequent clinical recurrences than HSV-2 3

Treatment Approaches

First Clinical Episode

• Recommended regimens for first clinical episodes (7-10 days): 2, 3
  • Valacyclovir 1 g orally twice daily
  • Acyclovir 400 mg orally three times daily
  • Acyclovir 200 mg orally five times daily
  • Famciclovir 250 mg orally three times daily
• Treatment may be extended if healing is incomplete after 10 days 2

Recurrent Episodes (Episodic Therapy)

• Recommended regimens for recurrent episodes (5 days): 2, 4
  • Valacyclovir 500 mg orally twice daily
  • Acyclovir 400 mg orally three times daily
  • Acyclovir 800 mg orally twice daily
  • Acyclovir 200 mg orally five times daily
  • Famciclovir 125 mg orally twice daily
• Episodic therapy is most effective when started during the prodrome or within 1 day after onset of lesions 4
• Patients should be provided with medication or a prescription to initiate treatment at the first sign of prodrome or genital lesions 3

Suppressive Therapy

• Daily suppressive therapy is recommended for patients with frequent recurrences (≥6 episodes per year) 1, 2
• Suppressive therapy options: 2, 3
  • Valacyclovir 1 g orally once daily
  • Valacyclovir 500 mg orally once daily
  • Acyclovir 400 mg orally twice daily
  • Famciclovir 250 mg orally twice daily
• Suppressive therapy reduces recurrence frequency by ≥75% and reduces asymptomatic viral shedding 2, 4
• After 1 year of continuous suppressive therapy, consider discontinuation to reassess recurrence frequency 2, 3
• Although suppressive therapy to prevent HSV-2 transmission was studied in heterosexual couples, it can be considered for all populations including MSM, women who have sex with women, and transgender persons 1
• Suppressive therapy is not effective to decrease transmission risk among persons with HIV/HSV-2 coinfection 1

Special Clinical Scenarios

HSV-1 vs HSV-2 Management

• The same medication dosages and frequencies are recommended for genital HSV-1 infection as for HSV-2 1
• No comparative data are available for treatment efficacy between genital HSV-1 vs HSV-2 infection, but based on biology and in vitro susceptibilities, no difference in efficacy is expected 1

Acyclovir-Resistant Genital Herpes

• Case reports suggest brincidofovir, imiquimod, and topical cidofovir may be useful in treating acyclovir-resistant HSV infections 1
• Clinical trials are ongoing for helicase-primase inhibitors for resistant cases 1

HSV Meningitis

• For first episode HSV-2 meningitis: acyclovir 10 mg/kg IV every 8 hours until resolution of fever and headache, followed by valacyclovir 1 g TID to complete a 14-day course 1
• For recurrent HSV-2 meningitis, oral therapy may be used for the entire course 1
• Important to distinguish HSV meningitis from HSV encephalitis, which requires 14-21 days of IV acyclovir 1

Patient Education and Counseling

• Inform patients that genital herpes is a recurrent, incurable viral disease; antiviral medications control symptoms but do not eradicate the virus 2, 5
• Advise patients to abstain from sexual activity when lesions or prodromal symptoms are present 2, 4
• Counsel patients that sexual transmission can occur during asymptomatic periods due to viral shedding 2, 5
• Advise patients to inform sex partners about having genital herpes and use condoms during all sexual exposures with new or uninfected partners 2, 3
• Approximately 20% of persons who are HSV-2 seropositive do not note genital symptoms consistent with genital herpes 1
• Asymptomatic viral shedding occurs more frequently in patients with HSV-2 infection than HSV-1 infection and in patients who have had genital herpes for less than 12 months 3

Important Clinical Considerations

• Topical acyclovir is substantially less effective than systemic therapy and is not recommended 2, 4
• Valacyclovir provides significantly better oral bioavailability than oral acyclovir, contributing to less frequent administration 6
• Antiviral resistance is rare in immunocompetent patients but more common in immunocompromised individuals 3
• Adequate hydration should be maintained during treatment 5, 7