Interpretation

Cytomegalovirus, also known as human herpesvirus 5, is a highly
ubiquitous, double-stranded DNA virus in
the Betaherpesvirinae subfamily. Serological studies have
demonstrated that a majority of adults in the United States have
been infected with CMV. Following primary
infection, CMV establishes a lifelong
latent infection, which may reactivate in both immunocompetent and
immunocompromised individuals. In immunocompromised patients,
primary or reactivated CMV infections can
cause a range of symptoms like fever and fatigue and diseases that
may include interstitial pneumonia, gastrointestinal infection,
central nervous system disease, hepatitis, retinitis, and
encephalitis. CMV reactivations have also
been reported to occur frequently in critically ill immunocompetent
patients and are associated with prolonged hospitalization or
death. Due to the severity of these conditions and even life
threatening outcomes, treatment of CMV
diseases with antiviral drugs is common. Additionally, prophylactic
treatment with antiviral drugs is used to prevent the occurrence of
disease in high-risk patients. Anti-CMV
drugs currently available for either treatment or prophylaxis
include ganciclovir, valganciclovir (the orally administered
prodrug), foscarnet, cidofovir, and letermovir. Ganciclovir targets
both UL97 and UL54, while cidofovir and foscarnet target only UL54.
The newest CMV drug, Letermovir, targets
subunit 2 of the viral terminase complex (UL56). Viral UL97
phosphotransferase gene, and UL54 polymerase genotypic mutations
are well documented mechanisms of resistance to these antiviral
drugs. Mutations within UL56 have been shown to confer resistance
to Letermovir. Drug resistance should be suspected if quantitative
CMV PCR viral
load values either persist or increase, or if CMV disease presents, after several weeks of
treatment with an appropriate dose.