Treatment of Genital Herpes
For first-episode genital herpes, treat with valacyclovir 1 gram orally twice daily for 7-10 days; for recurrent episodes, use valacyclovir 500 mg orally twice daily for 5 days; and for patients with ≥6 recurrences per year, initiate daily suppressive therapy with valacyclovir 1 gram once daily. 1, 2
First Clinical Episode
Initial infection requires 7-10 days of treatment to achieve clinical resolution, as this represents the most severe presentation with the highest viral burden. 3, 1
For severe disease requiring hospitalization (disseminated infection, pneumonitis, hepatitis, or CNS complications), use IV acyclovir 5-10 mg/kg every 8 hours for 5-7 days or until clinical resolution. 3, 1
For herpes proctitis specifically, higher doses are recommended: acyclovir 400 mg orally five times daily for 10 days. 1, 5
Recurrent Episodes: Episodic Therapy
Episodic therapy is most effective when initiated during the prodrome or within 24 hours of lesion onset—treatment started after this window has significantly reduced efficacy. 3, 1, 2
Valacyclovir offers superior convenience with twice-daily dosing compared to acyclovir's three-to-five times daily regimen, which improves adherence for prolonged treatment without sacrificing efficacy. 3, 6, 7
Suppressive Therapy
Daily suppressive therapy should be offered to all patients with ≥6 recurrences per year, as it reduces recurrence frequency by ≥75% and decreases asymptomatic viral shedding that can lead to transmission. 3, 1, 2
Valacyclovir 500 mg once daily is less effective than other dosing regimens in patients with very frequent recurrences (≥10 episodes per year), so use the 1 gram daily dose in this population. 3
Suppressive therapy is safe for extended use—up to 6 years with acyclovir and at least 1 year with valacyclovir and famciclovir. 1, 2, 4
After 1 year of suppressive therapy, consider discontinuation to reassess the patient's natural recurrence frequency, as recurrence rates often decrease over time. 3, 2
Special Populations
HIV-Infected and Immunocompromised Patients
Higher doses are required due to prolonged viral shedding and more severe disease presentation. 3, 1
- For recurrent episodes: Acyclovir 400 mg orally 3-5 times daily until clinical resolution 3, 1
- For suppressive therapy: Famciclovir 500 mg twice daily (shown to decrease both recurrences and subclinical shedding in HIV-infected patients) 3, 1
- For severe disease: IV acyclovir 5 mg/kg every 8 hours 1
Critical warning: Valacyclovir 8 grams per day is associated with hemolytic uremic syndrome/thrombotic thrombocytopenic purpura in immunocompromised patients and must be avoided. 3, 1, 2
Suppressive therapy does not reduce HSV-2 transmission risk in HIV/HSV-2 coinfected individuals, unlike in HIV-negative populations. 3
Acyclovir-Resistant Herpes
Suspect resistance if lesions fail to resolve within 7-10 days of appropriate antiviral therapy. 1, 2
- Resistance is rare in immunocompetent patients but more common in immunocompromised individuals 1, 5
- Treatment: Foscarnet 40 mg/kg IV every 8 hours for proven or suspected resistance 1, 2
- Emerging options include brincidofovir, imiquimod, and topical cidofovir, though clinical trial data are limited 3
Critical Clinical Pitfalls
Topical acyclovir is substantially less effective than oral therapy and should never be used, despite its FDA approval—this represents outdated practice. 3, 1, 2, 5
Treatment efficacy drops significantly if initiated >24 hours after symptom onset, so patient education about early self-initiation is essential. 1, 2
Genital HSV-1 and HSV-2 use identical treatment regimens, though HSV-1 recurs far less frequently (making suppressive therapy rarely necessary for HSV-1). 3
Suppressive therapy reduces but does not eliminate asymptomatic viral shedding, so transmission risk persists even on daily antivirals. 3, 1
Patient Counseling Requirements
Genital herpes is a recurrent, incurable viral disease—antivirals control symptoms but do not eradicate latent virus or prevent all future recurrences. 3, 1, 2
Abstain from sexual activity when lesions or prodromal symptoms are present, and use condoms during all sexual exposures with new or uninfected partners. 3, 1, 2, 5
Asymptomatic viral shedding occurs frequently (especially in the first 12 months after infection and with HSV-2 vs HSV-1), allowing transmission even without visible lesions. 3, 1, 2
Patients with persistent symptoms beyond 5 days of treatment warrant evaluation for treatment extension or potential co-infections. 1, 2