Treatment and prevention of cytomegalovirus infection in heart and lung transplantation: an update

ABSTRACT

Introduction: Heart and lung transplantation are standard therapeutic strategies to improve survival and quality of life in selected patients with end-stage heart or lung diseases. Cytomegalovirus (CMV) is one the most clinically relevant and frequent post-transplant infectious agents, which may cause direct acute syndromes, and chronic indirect graft-related injury. Despite effective antiviral drugs being available to prevent and treat CMV infection, due to the immunosuppression burden and the specific characteristics of thoracic grafts, CMV infection remains a major clinical problem in heart and lung transplant recipients.

Areas covered: We performed an extensive literature search focused on studies specifically including heart or lung transplantation, when available, or kidney transplant recipients when data on thoracic transplants were not available. We discuss the pros and cons supporting the use of currently available drugs and strategies for CMV prevention and treatment, highlighting current unmet needs.

Expert opinion: While (Val)Ganciclovir remains the cornerstone of anti-CMV therapy, prolonged universal prophylaxis may expose a large number of patients to an excess of drug toxicity. Additional drugs with lower toxicity may be available in the context of anti-CMV prophylaxis, and effective CMV-risk stratification, by means of novel immune monitoring assays, which may help to customize the therapeutic approach.

KEYWORDS:

• Cytomegalovirus
• ganciclovir
• heart transplant
• lung transplant
• prevention
• therapy

Article highlights

• Heart and Lung recipients are highly exposed to CMV infection risk

• Being lung a CMV latency site, viral infection is particularly harmful in lung transplant recipients.

• Viral reactivation has been associated with direct (organ damage) and indirect effects (acute rejection and chronic allograft dysfunction)

• Available evidence is unable to support which strategy among pre-emptive or prophylaxis is clearly superior but careful planning of CMV prevention strategy is mandatory for appropriate care of heart and lung recipients

• Ganciclovir and valganciclovir represent the pillar of antiviral drug therapy/prevention. Toxicity and viral resistances represent however a major issue to be considered

• Agents acting on the immune system such as CMV-Ig and mTOR inhibitors represent an effective therapeutic adjuvant approach to antiviral drugs

• Thanks to immune-monitoring assays, CMV management may further evolve to tailored approaches by matching, replication indexes, immunity status and immunosuppressive therapy.

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Declaration of interest

L Potena received advisory board fees from Biotest and an Institutional grant for an investigator-driven study by Qiagen. P Solidoro received advisory board fees from Biotest. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.