Antiviral resistance in CMV

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Background

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