What is the treatment for Epstein-Barr Virus (EBV)?

Treatment of Epstein-Barr Virus (EBV)

For most EBV infections, supportive care alone is the appropriate treatment, as antivirals like acyclovir are ineffective against EBV and should not be used. 1

Uncomplicated EBV Infection (Infectious Mononucleosis)

• Management focuses exclusively on symptom relief, adequate hydration, and rest until the self-limiting infection resolves. 1
• Antiviral drugs including acyclovir are completely ineffective against EBV and should never be prescribed for typical infectious mononucleosis. 1, 2
• While older research from 1988-1991 suggested minimal clinical benefit from acyclovir in reducing oropharyngeal viral shedding, current guidelines explicitly state these medications do not impact disease progression or symptoms and are not recommended. 3, 4

Chronic Active EBV Disease (CAEBV)

Hematopoietic stem cell transplantation is the only curative treatment for severe CAEBV and should be pursued when available. 5

Diagnostic Requirements Before Treatment:

• Persistent or recurrent symptoms (fever, lymphadenopathy, hepatosplenomegaly) for more than 3 months 5
• Markedly elevated antibody titers: VCA-IgG ≥1:640 and EA-IgG ≥1:160 5
• EBV DNA levels >10^2.5 copies/mg DNA in peripheral blood mononuclear cells 5

Treatment Approach:

• Allogeneic HSCT should be initiated early without watchful waiting, as 3-year overall survival is 87.3% with planned transplant versus only 16.7% with uncontrolled active disease. 6
• Supportive care with prednisolone and cyclosporine A with or without etoposide may provide temporary control while preparing for transplant. 6

EBV in High-Risk Populations (Post-Transplant)

Prophylaxis Strategy:

• EBV-specific cytotoxic T lymphocytes (CTLs) should be considered as first-line prophylactic treatment when available. 1, 2
• B-cell depletion with prophylactic rituximab may reduce the risk of EBV DNA-emia. 1
• All allogeneic HSCT patients and donors require EBV antibody testing before transplantation. 1
• Prospective monitoring of EBV DNA-emia by quantitative PCR is mandatory for at least 4 months post-transplant. 1, 2

Preemptive Therapy for EBV DNA-emia:

• Rituximab 375 mg/m² once weekly (1-4 doses) until EBV DNA-emia negativity is indicated for significant EBV DNA-emia without clinical symptoms. 1, 5, 2

EBV Post-Transplant Lymphoproliferative Disorder (PTLD)

Rituximab 375 mg/m² once weekly is the treatment of choice for EBV-PTLD, achieving positive outcomes in approximately 70% of patients. 1, 2

Treatment Algorithm:

• Combine rituximab with reduction of immunosuppressive therapy whenever possible. 1, 5, 2
• Administer 1-4 doses of rituximab weekly until response is achieved. 1, 2
• Consider donor or third-party EBV-specific CTLs if available. 1, 2

CNS EBV-PTLD Specific Management:

• Systemic or intrathecal rituximab ± chemotherapy based on primary CNS lymphoma protocols 1
• T-cell therapy with EBV-specific CTLs as an alternative option 1
• Radiotherapy may be considered for CNS disease 1

Critical Pitfalls to Avoid

• Never prescribe antivirals (acyclovir, valacyclovir, ganciclovir) for EBV—they are completely ineffective against latent or active EBV. 1, 2
• Do not rely on reduction of immunosuppression alone for PTLD after HSCT, as this is rarely successful and increases risk of graft-versus-host disease or rejection. 1, 2
• Avoid administering more than 4 doses of rituximab, as additional doses may cause down-regulation of CD20 expression and decreased efficacy. 1
• Do not use unselected donor lymphocyte infusions due to severe GvHD risk; previous GvHD is usually a contraindication. 1
• Recognize that EBV-negative B-PTLD presenting late (>5 years post-transplant) should be treated as malignant lymphoma with appropriate chemotherapy protocols, not as PTLD. 1

Special Populations

Immunocompromised Patients on Immunomodulatory Therapy:

• Reduce immunosuppression when possible in patients with EBV DNA-emia. 5
• Patients on thiopurines have increased risk of EBV-associated lymphoproliferative disorders. 5
• Consider temporary discontinuation of immunomodulators during acute primary EBV infection. 5

Past EBV Infection (Asymptomatic):

• No specific treatment or routine monitoring is recommended for immunocompetent individuals with past EBV infection (positive VCA IgG and EBNA IgG, negative VCA IgM). 2
• Regular monitoring of EBV DNA-emia may be warranted only in immunocompromised patients. 2