What is the recommended treatment for herpes simplex 2 (Genital Herpes)?

Treatment for Herpes Simplex 2 (Genital Herpes)

For first-episode genital HSV-2, start valacyclovir 1 g orally twice daily for 7-10 days; for recurrent episodes, use valacyclovir 500 mg twice daily for 5 days initiated within 24 hours of symptom onset; and for patients with ≥6 recurrences per year, prescribe daily suppressive therapy with valacyclovir 1 g once daily. 1

First Clinical Episode Treatment

The treatment approach differs significantly between first episodes and recurrent episodes, with first episodes requiring longer duration therapy.

• Valacyclovir 1 g orally twice daily for 7-10 days is the preferred first-line regimen due to convenient dosing and high bioavailability 1, 2
• Alternative regimens include acyclovir 400 mg orally three times daily for 7-10 days, acyclovir 200 mg orally five times daily for 7-10 days, or famciclovir 250 mg orally three times daily for 7-10 days 3, 1
• Treatment may be extended beyond 10 days if healing is incomplete 3, 1
• Higher doses of acyclovir (400 mg five times daily) may be needed for first-episode herpes proctitis or severe oral infection 3

Recurrent Episodes (Episodic Therapy)

Episodic therapy is most effective when initiated during the prodromal period or within 24 hours of lesion onset; delayed treatment beyond 72 hours significantly reduces effectiveness. 1

• Valacyclovir 500 mg orally twice daily for 5 days is the preferred regimen for recurrent episodes 1, 2
• Alternative regimens include acyclovir 400 mg orally three times daily for 5 days, acyclovir 800 mg orally twice daily for 5 days, acyclovir 200 mg orally five times daily for 5 days, or famciclovir 125 mg orally twice daily for 5 days 1, 4
• Patients should receive a prescription to self-initiate treatment at the first sign of recurrence 1
• Clinical trials demonstrate that valacyclovir reduces median time to lesion healing from 6 days (placebo) to 4 days and reduces viral shedding from 4 days to 2 days 2

Suppressive Therapy

Daily suppressive therapy should be considered for patients experiencing ≥6 recurrences per year, as it reduces recurrence frequency by ≥75% and reduces asymptomatic viral shedding. 1

• Valacyclovir 1 g orally once daily is the preferred suppressive regimen 1, 2
• Alternative regimens include valacyclovir 500 mg orally once daily (though may be less effective in patients with ≥10 episodes per year), acyclovir 400 mg orally twice daily, or famciclovir 250 mg orally twice daily 1, 4
• Valacyclovir is the only antiviral approved for once-daily suppressive dosing 5, 6
• After 1 year of suppressive therapy, consider discontinuation to reassess recurrence frequency 1
• Suppressive therapy reduces the risk of transmission to sexual partners by approximately 48% and reduces clinical disease in susceptible partners by 75% 1, 7

Comparative Effectiveness of Suppressive Agents

While all three agents are effective, valacyclovir appears somewhat superior to famciclovir for suppression of viral shedding. A head-to-head trial found HSV was detected on 1.3% of days with valacyclovir 500 mg daily versus 3.2% of days with famciclovir 250 mg twice daily (relative risk 2.33,95% CI 1.18-4.89) 8. This suggests valacyclovir may be the preferred agent when transmission prevention is a primary concern.

Special Populations

HIV-Infected Patients

• HIV-infected patients require closer monitoring and may need longer treatment courses than HIV-negative patients 3, 1
• For recurrent episodes in HIV-infected patients, use famciclovir 500 mg twice daily for 7 days or valacyclovir 500 mg twice daily for 7 days 1, 4
• Healing may be slower and treatment failures can occur with any regimen in this population 3

Patients with Renal Impairment

Dose adjustments are mandatory for patients with renal impairment to prevent acute renal failure, which has been reported with inappropriately high doses. 4

• For creatinine clearance 20-39 mL/min: reduce valacyclovir to 500 mg every 24 hours for recurrent episodes 4
• For creatinine clearance <20 mL/min: reduce to 250 mg every 24 hours 4
• For hemodialysis patients: administer 250 mg following each dialysis session 4
• Renal function monitoring is critical in elderly patients receiving antiviral therapy 1

Critical Clinical Considerations

Topical acyclovir is substantially less effective than systemic therapy and should not be used. 3, 1, 9

• Systemic antiviral drugs partially control symptoms but do not eradicate latent virus or affect subsequent recurrences after discontinuation 3, 1
• No laboratory monitoring is needed for patients on episodic or suppressive therapy unless substantial renal impairment exists 1
• Common side effects include nausea and headache 1

Treatment Failure and Resistance

If lesions do not begin to resolve within 7-10 days of appropriately dosed antiviral therapy, suspect acyclovir resistance.

• Obtain viral culture and perform susceptibility testing to confirm drug resistance 1
• For confirmed acyclovir-resistant HSV, IV foscarnet 40 mg/kg every 8 hours is the treatment of choice 1
• Acyclovir resistance is rare in immunocompetent patients but more common in immunocompromised hosts 1
• Consider alternative diagnoses including co-infection with another STD, HIV infection, or poor medication adherence 1

Transmission Prevention Counseling

Patients must be counseled to abstain from sexual activity when lesions or prodromal symptoms are present, as transmission can occur during these periods. 3, 1

• Consistent condom use reduces transmission risk to sexual partners by approximately 50% 1
• Asymptomatic viral shedding occurs intermittently even without visible lesions 3
• Suppressive antiviral therapy reduces but does not eliminate transmission risk 1, 7
• All patients should be informed about the chronic nature of HSV-2 infection and potential for recurrent episodes 3, 1