Prevention and management of CMV infection in pediatric solid organ transplant recipients

Abstract

Human cytomegalovirus (CMV) remains one of the most common opportunistic infections following solid organ transplantation in children. CMV causes morbidity and mortality through direct tissue-invasive disease and indirect immunomodulatory effects. In recent years, several new agents have emerged for the prevention and treatment of CMV disease in solid organ transplant recipients. However, pediatric data remain scarce, and many of the treatments are extrapolated from the adult literature. Controversies exist about the type and duration of prophylactic therapies and the optimal dosing of antiviral agents. This review provides an up-to-date overview of treatment modalities used to prevent and treat CMV disease in solid organ transplant (SOT) recipients.

A quick algorithmic review on management of viral infectious diseases in pediatric solid organ transplant recipients

“…Although secondary prophylaxis is not currently supported by good-quality data, some centers offer it after completion of treatment for 1–3 months to lower the chance of recurrence ( 24 ). Secondary prophylaxis may be helpful for children with recurrent CMV DNAemia or disease (≥2 episodes).…”

“…The UL97 kinase and UL54 DNA polymerase are two gene mutations that are associated with CMV drug resistance. Based on results of genotypic test, other antiviral agents such cidofovir and maribavir can be considered Maribavir is approved for treating post-transplant refractory CMV disease in pediatric patients who are at least 12 years old and weigh at least 35 kg ( 24 ).…”

Evaluation of Bispecific T-Cell Engagers Targeting Murine Cytomegalovirus

“…The current therapy options include antivirals such as (Val-) Ganciclovir [ 5 , 6 , 7 , 8 ] or Letermovir [ 9 , 10 ], and, recently, Maribavir, which are CMV- and herpes-virus-specific, respectively. They can be applied as a universal prophylaxis for patients at risk, or are used within pre-emptive prophylaxis regimes [ 11 ], as soon as a set viremia threshold is crossed [ 4 , 12 ]. However, adverse reactions, side effects, and emerging drug resistance complicate treatment [ 8 ].…”

“…In contrast to individualised therapies, BiTE provide a manufacturing process with easy storage for clinical application, similar to monoclonal antibodies or other biologicals. Additionally, interactions with classic drug metabolism pathways, such as Cytochrome P450 3A4 (CYP3A4), are not expected and, therefore, allow the safer combination with traditional drugs [ 11 ]. Highly promiscuous metabolisation enzymes such as CYP3A4 interact with up to 50% of the available drugs including antibiotics and immunosuppressants.…”