What is the recommended treatment for outpatient herpes simplex virus type 2 (HSV2)?

Outpatient HSV-2 Treatment

For first-episode genital HSV-2, treat with valacyclovir 1 g orally twice daily for 7-10 days; for recurrent episodes, use valacyclovir 500 mg orally twice daily for 5 days; and for patients with frequent recurrences (≥6 episodes per year), initiate daily suppressive therapy with valacyclovir 1 g orally once daily. 1, 2

First Clinical Episode

Treatment Duration and Regimens:

• Valacyclovir 1 g orally twice daily for 7-10 days is the preferred first-line therapy due to convenient dosing and effectiveness 2
• Alternative regimens include:
  • Acyclovir 400 mg orally three times daily for 7-10 days 2
  • Acyclovir 200 mg orally five times daily for 7-10 days 2
  • Famciclovir 250 mg orally three times daily for 7-10 days 2
• Extend treatment beyond 10 days if healing is incomplete 2, 3

Critical Counseling Points:

• Genital herpes is a recurrent, incurable viral disease that antiviral medications control but do not eradicate 1
• Asymptomatic viral shedding can occur, potentially leading to transmission even without visible lesions 1, 3
• Patients must abstain from sexual activity when lesions or prodromal symptoms are present 1, 2
• Consistent condom use reduces transmission risk by approximately 50% 2

Recurrent Episodes

Episodic Therapy:

• Valacyclovir 500 mg orally twice daily for 5 days is the preferred regimen 1, 2
• Alternative options include:
  • Acyclovir 400 mg orally three times daily for 5 days 1
  • Acyclovir 800 mg orally twice daily for 5 days 1
  • Acyclovir 200 mg orally five times daily for 5 days 1
  • Famciclovir 125 mg orally twice daily for 5 days 1

Timing is Critical:

• Start therapy during the prodrome or within 1 day after onset of lesions for maximum effectiveness 1, 2
• Delayed treatment beyond 72 hours significantly reduces effectiveness 2
• Median time to lesion healing with valacyclovir 500 mg is 4 days versus 6 days with placebo 4

Suppressive Therapy

Indications:

• Patients with ≥6 recurrences per year should be offered daily suppressive therapy 1, 2

Recommended Regimens:

• Valacyclovir 1 g orally once daily (preferred) 1, 2
• Valacyclovir 500 mg orally once daily (alternative for patients with 9 or fewer recurrences per year) 1, 4
• Acyclovir 400 mg orally twice daily 1, 2
• Famciclovir 250 mg orally twice daily 1, 2

Clinical Benefits:

• Reduces recurrence frequency by ≥75% 1, 2
• Reduces asymptomatic viral shedding 1, 2
• Reduces transmission risk to sexual partners 2
• Safe for up to 6 years with acyclovir and 1 year with valacyclovir 1

Management Strategy:

• After 1 year of suppressive therapy, consider discontinuation to reassess recurrence frequency 1, 2

Special Populations

HIV-Infected Patients:

• May require longer courses of therapy than HIV-negative patients 2
• In a trial of 293 HIV-infected adults, valacyclovir 500 mg twice daily for 6 months resulted in 65% remaining recurrence-free versus 26% with placebo 4
• Famciclovir 500 mg twice daily has been effective in reducing recurrences and subclinical shedding 2

Pregnant Women:

• Routine suppressive therapy is not recommended during pregnancy for recurrent genital herpes 1
• Safety of systemic acyclovir and valacyclovir in pregnancy has not been definitively established 1

Treatment Failure and Resistance

When to Suspect Resistance:

• If lesions do not begin to resolve within 7-10 days of therapy, suspect acyclovir resistance 1, 2
• Obtain viral culture and perform susceptibility testing to confirm drug resistance 2

Management of Resistant HSV:

• IV foscarnet 40 mg/kg every 8 hours is the treatment of choice for confirmed acyclovir-resistant HSV 1, 2

Other Causes of Treatment Failure:

• Consider incorrect diagnosis, co-infection with another STD, HIV infection, or poor medication adherence 2

Critical Clinical Pitfalls

Avoid These Common Errors:

• Never use topical acyclovir—it is substantially less effective than oral therapy 1, 2
• Do not use valacyclovir 8 g per day in immunocompromised patients—it is associated with hemolytic uremic syndrome/thrombotic thrombocytopenic purpura 1
• No laboratory monitoring is needed for patients on episodic or suppressive therapy unless substantial renal impairment exists 2

Common Side Effects:

• Nausea and headache are the most common side effects 2

HSV-1 Genital Infection Considerations

• HSV-1 accounts for 5-30% of first-episode genital herpes cases but causes significantly fewer recurrences than HSV-2 3
• Type-specific serologic testing to differentiate HSV-1 from HSV-2 has important prognostic value 3
• The same medication dosages and frequencies are recommended for genital HSV-1 as for HSV-2 2
• Suppressive therapy is rarely needed for HSV-1 genital infections due to infrequent recurrences 3