Current Management Strategies for the Treatment and Prevention of Cytomegalovirus Infection in Solid Organ Transplant Recipients

Abstract

Cytomegalovirus (CMV) infection in solid organ transplantation is associated with significant morbidity and mortality. Primary infection, secondary infection or superinfection may occur in this setting. Progression to disease may ensue with development of symptoms, with or without organ involvement. The mainstay of treatment of CMV disease is intravenous ganciclovir. Aside from protective organ matching and use of CMV-seronegative blood products, methods of preventing CMV infection and disease include passive immunisation with immunoglobulins, vaccination, and prophylaxis with antiviral agents such as aciclovir, oral or intravenous ganciclovir, and oral valaciclovir. A promising subunit vaccine is currently being investigated. Pre-emptive therapy is a form of prevention that is based either on the early detection of CMV or targeting of transplant recipients with risk factors for CMV. New sensitive laboratory assays, including the pp65 antigenaemia assay, qualitative, quantitative and reverse-transcription polymerase chain reaction assays, hybridisation assays, and nucleic acid sequence-based assays, have the ability to detect early CMV replication before disease becomes evident. These assays are being used as prospective surveillance tests, with pre-emptive therapy initiated when they become positive or demonstrate an increasing titre.

Pathogenicity and diagnostic methods of human cytomegalovirus

“…This assay employs RNA probes to identify and quantitatively measure the HCMV DNA. HCA enables early diagnosis and monitoring of antiviral therapy in AIDS patients and solid organ transplant recipients (Abu-Nader & Patel, 2000). Although HCA allows the simultaneous detection of viral DNA and RNA for quantitative purposes, it is less commonly used for HCMV detection due to its higher cost compared to other methods.…”

Valganciclovir for the prophylaxis and treatment of cytomegalovirus infection in solid organ transplantation

“…This assay offers both high specificity and high sensitivity and is useful in assessing the level of viral activity as well as response to therapy. 22,24 Another test that can be helpful in identifying when a patient may require pre-emptive antiviral therapy is the antigenemia assay, an immunoassay that quantifies the amount of virus by measuring the number of white blood cells containing viral particles and offers moderate sensitivity and specificity. 22 The antigenemia assay is less sensitive in patients with severe leukopenia as it requires the collection of a sufficient amount of peripheral blood neutrophils.…”

Efficacy and safety of conventional antiviral agents in preventive strategies for cytomegalovirus infection after kidney transplantation: a systematic review and network meta‐analysis

“…Antiviral agents including valganciclovir (VGC), valacyclovir (VAC), ganciclovir (GC), and acyclovir (AC) have been studied in prophylactic regimens or pre‐emptive regimens [ 11 , 12 , 13 , 14 ]. Although the third International Consensus Guidelines on the Management of CMV in Solid‐organ Transplantation [ 15 ], the Kidney Disease Improving Global Outcomes and clinical practice guidelines for KT [ 16 ] recommend that VGC and GC are considered as the first and second‐line drugs [ 17 , 18 ], in lower‐middle‐income countries, this has not been widely adopted given that VGC is high cost, has multiple adverse effects (e.g., anemia, neutropenia, leukopenia, thrombocytopenia, and hallucination) and limited healthcare infrastructures.…”