Does herpes simplex virus (HSV) require lifelong therapy?

Herpes Simplex Virus Does Not Require Lifelong Therapy

Herpes simplex virus (HSV) infection does not require lifelong therapy, as treatment approaches should be tailored based on frequency and severity of recurrences, with periodic reassessment of the need for continued suppressive therapy. 1

Understanding HSV Infection

• HSV is a recurrent, incurable viral disease that establishes latency in the dorsal root ganglion after initial infection 2
• Most patients with first-episode genital HSV-2 infection will experience recurrent episodes of genital lesions 1
• The frequency of recurrences varies greatly among individuals, with a median of four recurrences per year after the first episode 2
• HSV-2 recurs approximately six times more frequently than HSV-1 genital infections 2

Treatment Options for HSV

Episodic Therapy

For patients who experience occasional recurrences, episodic antiviral therapy is recommended:

• Treatment should be initiated during the prodrome or within 1 day after onset of lesions for maximum benefit 1
• Recommended regimens include:
  • Acyclovir 400 mg orally three times daily for 5 days 1, 3
  • Acyclovir 200 mg orally five times daily for 5 days 1, 3
  • Acyclovir 800 mg orally twice daily for 5 days 1, 3
  • Famciclovir 125 mg orally twice daily for 5 days 1, 3
  • Valacyclovir 500 mg orally twice daily for 5 days 1, 3

Suppressive Therapy

For patients with frequent recurrences (six or more per year), daily suppressive therapy is recommended:

• Suppressive therapy reduces recurrence frequency by ≥75% 1, 3
• Recommended regimens include:
  • Acyclovir 400 mg orally twice daily 1, 4
  • Famciclovir 250 mg orally twice daily 1
  • Valacyclovir 250 mg orally twice daily 1
  • Valacyclovir 500 mg orally once daily 1
  • Valacyclovir 1,000 mg orally once daily 1

Duration of Suppressive Therapy

• Safety and efficacy have been documented for daily therapy with acyclovir for up to 6 years, and with valacyclovir and famciclovir for 1 year 1
• After 1 year of continuous suppressive therapy, discontinuation should be considered to reassess the patient's recurrence rate 1, 4
• The FDA label for acyclovir specifically states that after 1 year of therapy, "the frequency and severity of the patient's genital herpes infection should be re-evaluated to assess the need for continuation of therapy" 4
• Many patients experience a decrease in recurrence frequency over time, potentially eliminating the need for continued suppressive therapy 1

Impact of Long-Term Suppressive Therapy

• Prolonged daily acyclovir suppressive therapy reduces humoral immunity to HSV, with mean IgG antibody concentration decreasing by 10% from baseline values after 1 year 5
• Another study found antibody levels declined by 27%-39% after one year of acyclovir therapy 6
• Despite these changes in antibody levels, suppressive therapy has not been associated with emergence of clinically significant acyclovir resistance among immunocompetent patients 1

Special Considerations

HIV Co-infection

• Patients with HIV may require more aggressive therapy and closer monitoring 1
• For HIV-infected persons with frequent or severe recurrences, daily suppressive therapy with acyclovir or famciclovir is recommended 1

Pregnancy

• In pregnant women with recurrent genital HSV, acyclovir prophylaxis might be indicated 1
• No pattern of adverse pregnancy outcomes has been reported after acyclovir exposure 1

Common Pitfalls and Caveats

• Suppressive treatment reduces but does not eliminate asymptomatic viral shedding, so transmission risk remains 1
• Topical acyclovir is substantially less effective than oral therapy and is not recommended 1
• Valacyclovir 500 mg once daily appears less effective for patients with very frequent recurrences (≥10 episodes per year) 1
• Patients should be counseled about the natural history of HSV, potential for recurrent episodes, asymptomatic viral shedding, and sexual transmission risk 1