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

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Last updated: June 22, 2025View editorial policy

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From the Guidelines

Treatment for Epstein-Barr Virus (EBV) infections should focus on managing symptoms and, in certain cases, preemptive therapy with rituximab, especially in patients with significant EBV DNA-emia without clinical symptoms of EBV disease. The approach to EBV infection management can be categorized into prophylaxis, pre-emptive therapy, and treatment of EBV disease or post-transplant lymphoproliferative disorders (PTLD) [ 1 ].

Management Strategies

For patients after allogeneic hematopoietic stem cell transplantation (HSCT), the management strategies include:

  • Prophylaxis: Interventions given to asymptomatic EBV-seropositive patients to prevent EBV DNA-emia.
  • Pre-emptive therapy: Interventions given to patients with EBV DNA-emia to prevent EBV disease.
  • Treatment of EBV disease: Therapeutic interventions for patients with probable or proven EBV disease.

Preemptive Therapy

Rituximab once weekly (1-4 doses) is recommended until EBV DNA-emia negativity [ 1 ]. This should be combined with reduction of immunosuppression, if possible. Donor or third-party EBV-specific cytotoxic T lymphocytes (CTL) should be considered if available [ 1 ].

First Line Therapy in EBV-PTLD

First line therapy includes:

  • Rituximab, 375 mg/m², once weekly.
  • Reduction of immunosuppressive therapy combined with rituximab, if possible.
  • Cellular therapy as adoptive immunotherapy with in vitro generated donor or third-party EBV-specific CTL, if available [ 1 ].

General Considerations

In general, for uncomplicated EBV infections, treatment primarily focuses on managing symptoms, including rest, adequate hydration, and over-the-counter pain relievers to reduce fever and alleviate sore throat and body aches. Patients should avoid strenuous physical activity and contact sports for at least 3-4 weeks to prevent potential splenic rupture, especially if splenomegaly is present. Corticosteroids may be prescribed in severe cases, but antiviral medications like acyclovir have not shown significant benefit for uncomplicated EBV infections [ 1 ].

From the Research

Treatment Options for Epstein-Barr Virus (EBV) Infections

  • The treatment for EBV infections varies depending on the severity and type of infection.
  • For severe EBV infections, various therapeutic approaches have been attempted, and some of them seem to be beneficial for certain EBV-associated diseases 2.
  • Acyclovir has been used as a potential treatment option for severe chronic active EBV (CAEBV) infections, with one case study showing a complete recovery with no deficits 3.
  • For chronic active EBV infection (CAEBV), the manifestations are often self-limiting with minimum supportive care or only prednisolone and cyclosporine A with or without etoposide. However, allogeneic hematopoietic stem cell transplantation (HSCT) is the only cure, without which patients with CAEBV die within several years 4.
  • Acyclovir administration has been shown to inhibit oropharyngeal EBV replication, but with minimal effect on clinical symptoms. The combination of intravenous acyclovir and prednisolone treatment has been effective in fulminant mononucleosis, causing transient cessation of virus shedding and a dramatic clinical effect on pharyngeal symptoms and fever 5.
  • For EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH), the optimal treatment strategy consists of three steps: control of cytokine storm, control of opportunistic infections, and eradication of clonally proliferating EBV-containing T- or NK-cells by immunochemotherapy and, if necessary, hemopoietic stem cell/bone marrow transplantation (SCT/BMT) 6.

References

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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