What is the first-line treatment for genital herpes?

First-Line Treatment for Genital Herpes

For first-episode genital herpes, the first-line treatment is oral antiviral therapy with valacyclovir 1 g twice daily for 7-10 days, which can be extended if healing is incomplete. 1

Initial Episode Management

Recommended first-line antiviral regimens for first clinical episodes include: 1

• Valacyclovir 1 g orally twice daily for 7-10 days (preferred due to convenient dosing) 1
• Acyclovir 400 mg orally three times daily for 7-10 days 1
• Acyclovir 200 mg orally five times daily for 7-10 days 1
• Famciclovir 250 mg orally three times daily for 7-10 days 1

Treatment should be extended beyond 10 days if healing remains incomplete. 1 For severe disease requiring hospitalization, intravenous acyclovir 5-10 mg/kg every 8 hours for 5-7 days or until clinical resolution is recommended. 1

Key Clinical Considerations for Initial Episodes

• Higher acyclovir dosages may be required in immunocompromised patients. 1
• Topical acyclovir is substantially less effective than oral therapy and should not be used. 2, 1
• Clinical trials demonstrate that valacyclovir 1 g twice daily achieves median time to lesion healing of 9 days, median time to cessation of pain of 5 days, and median time to cessation of viral shedding of 3 days—equivalent to acyclovir 200 mg five times daily. 3

Recurrent Episode Management

For recurrent genital herpes, episodic therapy with valacyclovir 500 mg orally twice daily for 5 days is first-line treatment. 2, 1

Alternative episodic therapy options include: 2, 1

• Acyclovir 400 mg orally three times daily for 5 days 2
• Acyclovir 800 mg orally twice daily for 5 days 2
• Acyclovir 200 mg orally five times daily for 5 days 2
• Famciclovir 125 mg orally twice daily for 5 days 2

Optimizing Episodic Therapy

Episodic therapy is most effective when initiated during the prodrome or within 1 day after onset of lesions. 2, 1 Patients should be provided with medication or a prescription to self-initiate treatment at the first sign of prodrome or genital lesions. 1

Clinical trial data show that valacyclovir 500 mg twice daily for 5 days reduces median time to lesion healing to 4 days versus 6 days with placebo, and median time to cessation of viral shedding to 2 days versus 4 days with placebo. 3 A 3-day course of valacyclovir 500 mg twice daily achieves similar efficacy to the 5-day regimen, with median time to lesion healing of approximately 4.5 days in both groups. 3

Suppressive Therapy for Frequent Recurrences

For patients with frequent recurrences (≥6 episodes per year), daily suppressive therapy with valacyclovir 1 g orally once daily is recommended. 2, 1

Alternative suppressive therapy regimens include: 2, 1

• Valacyclovir 500 mg orally once daily 2, 1
• Acyclovir 400 mg orally twice daily 2, 1
• Famciclovir 250 mg orally twice daily 2, 1

Benefits and Duration of Suppressive Therapy

Suppressive therapy reduces recurrence frequency by ≥75% and reduces asymptomatic viral shedding. 2, 1 Safety and efficacy have been documented for acyclovir for up to 6 years and for valacyclovir and famciclovir for 1 year. 1

In immunocompetent adults, valacyclovir 1 g once daily achieves 55% recurrence-free rate at 6 months and 34% at 12 months, compared to 7% and 4% with placebo, respectively. 3 In HIV-1-infected adults on stable antiretroviral therapy, valacyclovir 500 mg twice daily achieves 65% recurrence-free rate at 6 months versus 26% with placebo. 3

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

Critical Pitfalls to Avoid

• Never use topical acyclovir—it is substantially less effective than oral therapy. 2, 1
• Avoid valacyclovir 8 g per day in immunocompromised patients due to risk of hemolytic uremic syndrome/thrombotic thrombocytopenic purpura. 2
• Suspect acyclovir resistance if lesions do not begin to resolve within 7-10 days of therapy; consider foscarnet 40 mg/kg IV every 8 hours for proven or suspected resistance. 2
• Routine suppressive therapy is not recommended during pregnancy for recurrent genital herpes, though the safety of systemic acyclovir and valacyclovir in pregnancy has not been definitively established. 2

Essential Patient Counseling

Patients must understand that: 2, 1

• Genital herpes is a recurrent, incurable viral disease 2
• Antiviral medications control symptoms but do not eradicate the virus or prevent all recurrences 2, 1
• Asymptomatic viral shedding can occur, potentially leading to transmission 2, 1
• They should abstain from sexual activity when lesions or prodromal symptoms are present 2, 1
• They should inform sex partners about having genital herpes 2, 1
• They should use condoms during all sexual exposures with new or uninfected partners 2, 1
• HSV-2 causes more frequent asymptomatic shedding than HSV-1, and shedding is more frequent in the first 12 months after infection 1

Special Population Considerations

For immunocompromised patients, higher doses may be required (acyclovir 400 mg orally three to five times daily until clinical resolution, or IV acyclovir 5-10 mg/kg every 8 hours). 4 Pregnant women with genital herpes should inform their healthcare providers about the HSV infection. 1