What is the recommended prophylaxis for Herpes Simplex Virus (HSV)?

HSV Prophylaxis Recommendations

Acyclovir, valacyclovir, or famciclovir are the recommended first-line agents for HSV prophylaxis in high-risk populations, with the specific regimen determined by the patient's clinical context and immunosuppression status. 1

High-Risk Populations Requiring HSV Prophylaxis

• HSV-seropositive patients with acute leukemia undergoing induction or reinduction chemotherapy should receive prophylaxis during periods of neutropenia 1
• Hematopoietic cell transplant (HCT) recipients who are HSV-seropositive should receive prophylaxis during neutropenia and possibly longer depending on immunosuppression level 1
  • Allogeneic HCT recipients with graft-versus-host disease (GVHD) require extended prophylaxis 1
  • Autologous HCT recipients should receive prophylaxis during neutropenia 1
• Patients with chronic lymphocytic leukemia treated with alemtuzumab should receive prophylaxis until at least 2 months after completion of therapy and until CD4+ counts reach ≥200 cells/mcL 1
• Patients with intermediate risk for HSV reactivation including those with:
  • Hematologic malignancies with prolonged neutropenia 1
  • Those receiving high-dose corticosteroids 1
  • Those receiving T-cell-depleting agents (e.g., fludarabine) 1
• Patients with prior HSV reactivation requiring treatment should receive prophylaxis during all future episodes of neutropenia induced by cytotoxic therapy 1
• HSV-seropositive children undergoing cancer treatment should receive prophylaxis 1

Recommended Prophylactic Agents

• First-line agents:
  • Acyclovir
  • Valacyclovir
  • Famciclovir 1
• For acyclovir-resistant HSV infection:
  • Foscarnet is the agent of choice 1
• Special considerations:
  • Patients receiving ganciclovir or foscarnet for CMV prophylaxis do not need additional HSV prophylaxis as these agents are active against HSV 1
  • Patients receiving letermovir for CMV prophylaxis require additional HSV prophylaxis as letermovir lacks activity against HSV 1

Duration of Prophylaxis

• Acute leukemia patients: During period of neutropenia 1
• Allogeneic HCT recipients: During neutropenia and possibly longer; extended prophylaxis for those with GVHD or frequent pre-transplant HSV reactivations 1
• Autologous HCT recipients: During neutropenia 1
• Alemtuzumab-treated patients: Until at least 2 months after completion of therapy and until CD4+ counts reach ≥200 cells/mcL 1

Clinical Importance of HSV Prophylaxis

• Without prophylaxis, HSV reactivation occurs in 60-80% of seropositive HCT recipients and acute leukemia patients undergoing induction/reinduction therapy 1
• HSV reactivation can cause significant mucosal damage, resulting in:
  • Increased pain
  • Limited ability to maintain oral hydration and nutrition
  • Increased risk of bacterial and fungal superinfections 1, 2
• Disseminated HSV infection, while uncommon, can be life-threatening in immunocompromised patients 2

Common Pitfalls and Caveats

• Failure to screen: HSV serology should be checked before starting immunosuppressive therapy to identify patients who would benefit from prophylaxis 3
• Inadequate duration: Prophylaxis duration should be tailored to the degree and duration of immunosuppression 1
• Asymptomatic shedding: Even with suppressive therapy, asymptomatic viral shedding may occur, potentially leading to transmission 4
• Drug resistance: Acyclovir-resistant HSV can emerge, especially in immunosuppressed patients; foscarnet is the alternative in these cases 2, 5
• Confusing HSV and VZV prophylaxis: While the same agents are used, VZV prophylaxis typically requires higher doses and longer duration than HSV prophylaxis 1

Special Populations

• HIV-infected individuals: For those with frequent or severe HSV recurrences, daily suppressive therapy with acyclovir, famciclovir, or valacyclovir is recommended 1
• Pregnant women: Antiviral prophylaxis decisions should be individualized after specialist consultation; acyclovir prophylaxis may be indicated for those with frequent, severe recurrences of genital HSV 1
• Pediatric patients: HSV prophylaxis is indicated in HSV-seropositive children undergoing cancer treatment; dosing should be adjusted based on age and weight 1, 6