Cytomegalovirus (CMV) is the major opportunistic virus encountered after organ transplantation, and resistant variants can make antiviral treatment challenging. ARUP is introducing three new tests to detect CMV drug resistance using next generation sequencing (NGS). These tests will detect variants present in the CMV viral genes UL27, UL97, UL54, and UL56.

Specific variants present in these genes are associated with antiviral resistance. Increasing or stable viral loads in a patient receiving antiviral therapy may indicate the presence of drug-resistant viral populations.1 NGS technology allows a deeper discrimination of the emergence and persistence of a drug-resistance mutation.

Indications for Testing

Two classes of molecular CMV tests are key to the successful management of CMV. First is the quantitative molecular test that identifies concentrations of CMV virus due to active infections. The second class is the sequencing tests used to identify antiviral drug-associated resistance variants that, when present even at low concentrations, may continue to evolve and ultimately lead to treatment failure. The detection and identification of drug-resistant virus populations is essential for informing optimal therapy.

Choosing a Test

ARUP offers multiple tests that determine CMV drug resistance depending on the drug(s) of interest. Effective November 7, 2022, the following tests will be available:

Test Name ARUP Test Code

Sequencing
Method

Genes
Sequenced
Antiviral Drug Resistance Reported Limit of Detection

Cytomegalovirus Drug Resistance by Next Generation Sequencing, Ganciclovir, Foscarnet, Cidofovir, and Maribavir

3004508

NGS

UL97
UL54
UL27

Ganciclovir
Foscarnet
Cidofovir
Maribavir

Mutations <10% of total population may not be detected

Cytomegalovirus Drug Resistance by Next Generation Sequencing, Letermovir

3004509

NGS

UL56

Letermovir

Mutations <10% of total population may not be detected

Cytomegalovirus Drug Resistance by Next Generation Sequencing, Ganciclovir, Foscarnet,Cidofovir, Maribavir and Letermovir

3004615

NGS

UL97
UL54
UL27
UL56

Sequencing, Ganciclovir, Foscarnet, Cidofovir, Maribavir, and Letermovir

Mutations <10% of total population may not be detected

Cytomegalovirus Antiviral Drug Resistance by Sequencing

2004760

Polymerase Chain Reaction/Sequencing

UL97
UL54

Ganciclovir
Cidofovir
Foscarnet

Mutations <20% of total population may not be detected

Why Use ARUP Laboratories?

ARUP’s NGS testing offers the following:

  • The NGS testing has high sensitivity and can detect viral populations as low as 10% of the total viral population. The NGS testing is more sensitive than ARUP’s current test, Cytomegalovirus Antiviral Drug Resistance by Sequencing 2004760, with a limit of detection that is lower than some competitor’s assays.
  • ARUP’s testing can determine resistance-associated variants in multiple genes (UL97, UL54, UL27, and UL56). More genes are sequenced compared to some competitor’s assays.
  • ARUP offers multiple testing options that determine CMV drug resistance depending on the drug(s) of interest.
  • Drug resistance is determined using a database of published resistance mutations.

3004508

Cytomegalovirus Drug Resistance by Next Generation Sequencing, Ganciclovir, Foscarnet, Cidofovir, and Maribavir

3004509

Cytomegalovirus Drug Resistance by Next Generation Sequencing, Letermovir

3004615

Cytomegalovirus Drug Resistance by Next Generation Sequencing, Ganciclovir, Foscarnet, Cidofovir, Maribavir, and Letermovir

Additional Resources/Information

Cytomegalovirus Antiviral Drug Resistance by Sequencing, 2004760, is New York approved.

The CMV drug resistance by NGS testing is not currently New York approved. Please call ARUP Client Services for current status.

For more information on testing options, visit the ARUP Consult Cytomegalovirus - CMV topic.

References

  1. Kotton CN, et al. The Third International Consensus Guidelines on the management of cytomegalovirus in solid-organ transplantation. Transplantation. 2018;102(6):900-931.