CHARMD

TOP

Antiviral:

Each impacted antiviral is indicated, with the corresponding IS50. Empty boxes mean no impact.

EC50 ratio (IS50, sensitivity index):

Fold increase in EC50 associated with the mutation (EC50 of Mutant virus/EC50 of reference wild-type strain(s) tested in the recombinant phenotyping assay). For natural polymorphisms EC50 ratio value is arbitrary 1. For other mutations EC50 ratio with standard deviations when available is indicated.

CNR guidelines for interpretation:

The EC50 ratio threshold used for resistance is 2.0 as recently described in Chou et al. 2024 (JID)*
Mutans are classified as follow:

• EC50 ratio < 0.5: possible hypersensitivity, no resistance
• 0.5 < EC50 ratio < 2.0: no resistance
• 2.0 < EC50 ratio < 3: low level resistance
• 3 < EC50 ratio < 5: intermediate level resistance
• 5 < EC50 ratio: high level resistance

If intermediate or high-level resistance the antiviral concerned should not be used.
In case of low-level resistance to ganciclovir increasing dosage using intravenous administration can be attempted (Kotton et al., 2018).
Mutants increasing viral replicative capacity without resistance are indicated as “increased fitness”. These mutants may be associated with non-response to treatment or relapse.


* The EC50 ratio threshold is described in the publication as 1.9. It was set to 2 after consortium expertise.