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 3-5 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)
Valacyclovir is the preferred agent due to superior dosing convenience compared to acyclovir, with equivalent efficacy. 1, 2
Preferred regimen: Valacyclovir 1 gram orally twice daily for 7-10 days 1, 2, 3
Alternative regimens include:
Therapy is most effective when initiated within 48 hours of symptom onset 1, 3
Treatment may be extended beyond 10 days if healing is incomplete 2
For herpes proctitis specifically, use acyclovir 400 mg orally 5 times daily for 10 days 4, 5
Recurrent Episodes: Episodic Treatment
Patient-initiated therapy at the first sign of prodrome or lesions is critical for efficacy—treatment after 24 hours significantly reduces benefit. 1
Preferred regimen: Valacyclovir 500 mg orally twice daily for 3-5 days 1, 2, 3
Alternative regimens include:
Patients should be provided with medication or a prescription in advance to enable immediate self-initiation at symptom onset 2
The 3-day valacyclovir regimen is FDA-approved and equally effective as the 5-day regimen 3
Daily Suppressive Therapy (≥6 Recurrences Per Year)
Suppressive therapy reduces recurrence frequency by ≥75% and is safe for extended use up to 6 years. 1, 2, 5
Preferred regimen: Valacyclovir 1 gram orally once daily 1, 2, 5, 3
Alternative regimens include:
After 1 year of continuous suppressive therapy, consider discontinuation to reassess recurrence frequency 4, 2
Valacyclovir is the only antiviral approved for once-daily suppressive dosing, improving adherence 1, 6
Suppressive therapy does not eliminate asymptomatic viral shedding or completely prevent transmission 4
Severe Disease Requiring Hospitalization
For disseminated infection, encephalitis, pneumonitis, hepatitis, or other complications necessitating hospitalization, use intravenous acyclovir. 4, 1, 2
- Recommended regimen: Acyclovir 5-10 mg/kg IV every 8 hours for 5-7 days or until clinical resolution 4, 1, 2, 5
Special Populations
HIV-Infected/Immunocompromised Patients
- For suppressive therapy in HIV-infected patients with CD4+ count ≥100 cells/mm³, use valacyclovir 500 mg orally twice daily 1, 3
- Higher doses are required for episodic treatment: acyclovir 400 mg orally 3-5 times daily until clinical resolution 1, 2
- Famciclovir 500 mg orally twice daily for 7 days is effective for recurrent episodes in HIV-infected patients 1, 2
- Severe cases require IV acyclovir 5 mg/kg every 8 hours 1
- Avoid valacyclovir doses ≥8 grams per day due to risk of hemolytic uremic syndrome/thrombotic thrombocytopenic purpura 1
Acyclovir Resistance
- Suspect resistance if lesions fail to resolve within 7-10 days of appropriate therapy 1
- Resistance is rare in immunocompetent patients but more common in immunocompromised individuals, particularly those with HIV 1, 2, 5
- For proven or suspected resistance, use foscarnet 40 mg/kg IV every 8 hours 1, 2
Pregnancy
- Oral acyclovir may be used for first episodes during pregnancy, though safety data remain limited 2
- Women receiving acyclovir or valacyclovir during pregnancy should be reported to the manufacturer's pregnancy registry 2
- Acyclovir prophylaxis from 36 weeks gestation until delivery is recommended for women with a history of genital herpes 7
Critical Clinical Pitfalls
- Topical acyclovir is substantially less effective than oral therapy and should never be used 1, 2, 5
- Treatment initiated after 24 hours of symptom onset has significantly reduced efficacy—emphasize early self-initiation to patients 1
- Valacyclovir and famciclovir offer comparable efficacy to acyclovir but with superior dosing convenience, improving adherence for prolonged treatment 1, 6
Essential Patient Counseling
- Genital herpes is a recurrent, incurable viral disease—antiviral medications control symptoms but do not eradicate the virus or prevent all recurrences 1, 2
- Abstain from sexual activity when lesions or prodromal symptoms are present 4, 1, 2, 5
- Use condoms during all sexual exposures with new or uninfected partners 4, 1, 2, 5
- Asymptomatic viral shedding can occur and lead to transmission even without visible lesions—this occurs more frequently with HSV-2 than HSV-1 and in the first 12 months after infection 1, 2
- Inform sex partners about having genital herpes 2
- Women of childbearing age should inform healthcare providers about their HSV infection if they become pregnant 4, 2
- Persistent symptoms beyond 5 days warrant evaluation for treatment extension or potential co-infections 1