What is the recommended treatment for a patient with a history of genital herpes outbreaks due to Herpes Simplex Virus 2 (HSV2) for suppression?

HSV-2 Suppression Therapy

For patients with recurrent genital HSV-2 infection, daily suppressive therapy with valacyclovir 1 gram once daily is the first-line recommendation, reducing recurrence frequency by ≥75% and decreasing transmission risk to uninfected partners. 1, 2, 3

Indications for Suppressive Therapy

• Daily suppressive therapy should be initiated in patients experiencing ≥6 recurrences per year. 4, 1, 2
• Suppressive therapy reduces recurrence frequency by ≥75% compared to no treatment. 4, 1, 2
• Beyond symptom control, suppressive therapy decreases asymptomatic viral shedding, which reduces transmission risk to sexual partners by approximately 48%. 1, 5
• Long-term safety has been documented for up to 6 years with acyclovir and 1 year with valacyclovir and famciclovir. 4, 1

Recommended Suppressive Regimens

First-line options:

• Valacyclovir 1 gram orally once daily (preferred for most patients with normal immune function). 4, 2, 3
• Valacyclovir 500 mg orally once daily (alternative for patients with <10 recurrences per year, though may be less effective in those with ≥10 episodes annually). 4, 2, 3, 6
• Acyclovir 400 mg orally twice daily (alternative option with extensive safety data). 4, 2
• Famciclovir 250 mg orally twice daily (alternative with comparable efficacy). 4, 2

The once-daily valacyclovir regimen offers superior convenience and may improve adherence compared to twice-daily dosing. 1, 3, 6

Dosing Considerations Based on Recurrence Frequency

• For patients with <10 recurrences per year: Valacyclovir 500 mg once daily is adequate. 3, 6
• For patients with ≥10 recurrences per year: Valacyclovir 1 gram once daily or 500 mg twice daily provides superior efficacy. 7, 6
• The FDA-approved dosing for suppression is 1 gram once daily, with 500 mg once daily as an alternative for those with ≤9 recurrences per year. 3

Special Population: HIV-Infected Patients

• In HIV-infected patients with CD4+ counts ≥100 cells/mm³, the recommended dosage is valacyclovir 500 mg twice daily (not once daily). 3
• This higher frequency dosing is necessary due to increased viral reactivation in immunocompromised states. 3

Transmission Reduction Strategy

• For immunocompetent patients specifically concerned about transmitting HSV-2 to an uninfected heterosexual partner, valacyclovir 500 mg once daily reduces transmission risk by 48% and clinical disease in the susceptible partner by 75%. 3, 5
• This indication requires that the source partner has ≤9 recurrences per year. 3
• Suppressive therapy must be combined with safer sex practices, including consistent condom use and abstinence during prodromal symptoms or active lesions. 4, 1, 2

Reassessment Strategy

• After 1 year of continuous suppressive therapy, discontinue treatment temporarily to reassess the patient's natural recurrence frequency. 1, 2
• Many patients experience decreased recurrence rates over time, and some may no longer require daily suppressive therapy. 1
• If recurrences remain frequent (≥6 per year), resume suppressive therapy. 1

Critical Counseling Points

• Patients must understand that asymptomatic viral shedding occurs even on suppressive therapy, though at reduced rates. 4, 1, 2
• HSV-2 causes more frequent asymptomatic shedding than HSV-1, making transmission counseling particularly important. 4, 7
• Patients should abstain from sexual activity when prodromal symptoms (tingling, burning) or visible lesions are present. 4, 1, 2
• All patients, including men, should be counseled about neonatal transmission risk, and women of childbearing age must inform obstetric providers of their HSV-2 status. 4, 1, 7

Episodic Therapy Alternative

• For patients who decline suppressive therapy or have <6 recurrences per year, provide a prescription for episodic treatment to self-initiate at first prodromal symptoms. 4, 1, 2
• Episodic regimens include valacyclovir 500 mg twice daily for 3 days, acyclovir 400 mg three times daily for 5 days, or famciclovir 125 mg twice daily for 5 days. 2, 3, 8
• Treatment must be initiated within 24 hours of symptom onset for maximum efficacy; delaying beyond 72 hours significantly reduces effectiveness. 1, 7

Common Pitfalls to Avoid

• Never use topical acyclovir alone—it is substantially less effective than systemic therapy. 1, 2, 7
• Do not initiate suppressive therapy in patients with <6 recurrences per year, as the benefit does not justify continuous medication. 1, 2
• Avoid valacyclovir 8 grams per day in immunocompromised patients due to risk of hemolytic uremic syndrome/thrombotic thrombocytopenic purpura. 2
• If lesions fail to resolve within 7-10 days of therapy, suspect acyclovir resistance and consider foscarnet 40 mg/kg IV every 8 hours. 2
• Routine suppressive therapy during pregnancy for recurrent genital herpes is not recommended, though episodic treatment remains appropriate. 2