What is the recommended daily suppressive antiviral regimen for a patient with recurrent genital HSV‑2 to reduce outbreak frequency and viral shedding?

HSV-2 Suppressive Therapy

For immunocompetent adults with recurrent genital HSV-2, the recommended daily suppressive regimen is valacyclovir 500 mg once daily for patients with fewer than 10 recurrences per year, or valacyclovir 1000 mg once daily for those with 10 or more recurrences per year. 1

Recommended Suppressive Regimens by Recurrence Frequency

Standard Dosing for Immunocompetent Adults

• Valacyclovir 500 mg once daily is the CDC-recommended regimen for patients experiencing fewer than 10 recurrences annually. 1

• Valacyclovir 1000 mg (1 gram) once daily should be used for patients with frequent recurrences (≥10 episodes per year), as the 500 mg dose is less effective in this population. 1

• Acyclovir 400 mg twice daily is an effective alternative with documented safety for up to 6 years of continuous use, though it requires twice-daily dosing. 12

• Famciclovir 250 mg twice daily provides comparable efficacy to acyclovir with at least 1 year of documented safety data. 1

Special Population: HIV-Infected Patients

• HIV-infected patients with CD4+ counts ≥100 cells/mm³ require valacyclovir 500 mg twice daily—once-daily dosing is inadequate in this population. 13

• Twice-daily dosing of any antiviral (acyclovir or famciclovir) is preferred over once-daily regimens in HIV-infected individuals. 1

• Suppressive therapy in HIV-infected persons reduces HIV RNA concentrations in both plasma and genital secretions, though the direct clinical benefit of this reduction remains uncertain. 1

Clinical Benefits and Efficacy

• Daily suppressive therapy reduces recurrence frequency by ≥75% in patients with frequent episodes (≥6 recurrences per year). 12

• Suppressive therapy significantly lowers asymptomatic viral shedding, which is the primary mode of HSV-2 transmission, though it does not eliminate shedding completely. 14

• All HSV-2-infected patients should be offered a discussion of suppressive therapy as a management option, regardless of recurrence frequency. 1

• Valacyclovir 500 mg once daily is FDA-approved for reduction of transmission in heterosexual discordant couples, reducing symptomatic HSV-2 acquisition by 75% and overall acquisition by 48%. 34

Duration of Therapy and Reassessment Strategy

• After 1 year of continuous suppressive therapy, clinicians should discuss discontinuation with the patient to reassess recurrence frequency, as outbreak rates often decline naturally over time. 12

• Safety and efficacy have been documented for 1 year with valacyclovir and up to 6 years with acyclovir in continuous suppressive use. 1

• Many individuals experience a natural reduction in recurrence frequency after several years of infection, supporting periodic evaluation of ongoing need for suppression. 1

Renal Dosing Adjustments

• No dose adjustment is required for creatinine clearance (CrCl) 30–49 mL/min. 1

• For CrCl <30 mL/min, reduce valacyclovir to 500 mg every 24–48 hours. 1

• Routine laboratory monitoring is not needed for patients on suppressive therapy unless substantial renal impairment is present. 1

Critical Pitfalls to Avoid

• Topical acyclovir should never be used as it is substantially less effective than systemic therapy and does not provide adequate suppression. 12

• Valacyclovir 8 grams per day must be avoided in immunocompromised patients due to risk of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), though this has not been reported at standard HSV suppression doses. 12

• HIV-infected patients require twice-daily dosing—prescribing once-daily valacyclovir 500 mg or 1000 mg is inadequate and represents a common prescribing error. 1

Management of Treatment Failure

• If lesions persist or fail to improve within 7–10 days despite appropriate valacyclovir therapy, suspect acyclovir resistance. 12

• All acyclovir-resistant HSV strains are also resistant to valacyclovir due to cross-resistance. 1

• For proven or suspected acyclovir-resistant HSV, intravenous foscarnet 40 mg/kg every 8 hours until clinical resolution is the treatment of choice. 12

• Resistance rates in immunocompetent patients remain extremely low (<0.5%), but rise to 5–7% in immunocompromised individuals. 1

Patient Counseling Essentials

• Patients must understand that suppressive therapy does not eliminate asymptomatic viral shedding or transmission risk—it only reduces both. 12

• Patients should abstain from sexual activity during active lesions or prodromal symptoms and use condoms during all sexual encounters with new or uninfected partners. 12

• Women of childbearing age should disclose any history of genital herpes to healthcare providers before or during pregnancy to allow appropriate neonatal risk mitigation. 1

• Genital herpes is a chronic, incurable viral infection—antiviral medications control symptoms but do not eradicate the virus or prevent all recurrences. 2