Antiviral resistance in CMV
From IDWiki
Background
- Inherent resistance to acyclovir
- Acquired resistance to ganciclovir, foscarnet, cidofovir, and letermovir is possible
| Gene | Product | Mutations | Resistance | Notes |
|---|---|---|---|---|
| UL97 | kinase | M460V, H520Q, A594V, L595S, C603W, L595F | high-level ganciclovir | most common (0-3% of transplant recipients) |
| M460I, C592G, L595W | low-level ganciclovir | |||
| L405P, M460T, V466G, A594T/P/G/E, L595S, E596G, G598S, K599T, C603W/R/S, C607Y/F, Δ591-594, Δ591-607, Δ595, Δ595-603, Δ600, Δ601, Δ601-603 | ganciclovir | |||
| V353A, L397R, T409M, H411Y/N/L | maribavir | |||
| UL54 | DNA polymerase | D301N, N408D/K, N410K, F412C/V, D413A/E, L501I, T503I, K513E/N, L516R, I521T, P522A/S, L545S, A987G | ganciclovir and cidofovir | |
| N495K, D588E, E756D/Q, T700A, V715M, T838A | foscarnet | |||
| L776M, V781I, V787L, L802M, A809V | foscarnet and ganciclovir | |||
| D588N, E756K, V812L, T813S, A834P, G841A, Δ981-2 | foscarnet, ganciclovir, and cidofovir | |||
| K805Q | cidofovir | |||
| UL56 | terminase complex | mutations in the codon range 231-369 | letermovir | |
| UL51 | terminase complex | letermovir | ||
| UL89 | terminase complex | letermovir |
Clinical Manifestations
- CMV viral load increasing or failing to decrease after 2 weeks of appropriate antiviral therapy
- Failure to improve clinically after 2 weeks of appropriate antiviral therapy
Diagnosis
- Genotyping for resistance alleles
Management
- Decrease immunosuppression, if possible
- If switching to foscarnet or cidofovir, monitor closely for renal toxicity
