Analysis of cytomegalovirus DNA polymerase (UL54) mutations in solid organ transplant patients receiving valganciclovir or ganciclovir prophylaxis

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Abstract
We previously reported the absence of CMV UL97 (kinase) gene resistance mutations up to 12 months post‐transplant following 100 days of valganciclovir prophylaxis, and a low incidence of resistance mutations following 100 days of oral ganciclovir prophylaxis in a prospective multicenter study in solid organ transplant recipients excluding lung transplants. Herein, we report UL54 (DNA polymerase) gene sequencing results for all patients with previous UL97 PCR‐positive samples (n = 99) in our study. One UL54 resistance mutation (L545S known to confer ganciclovir and cidofovir resistance) was detected in a routine day‐100 sample from an asymptomatic patient who received oral ganciclovir. Notably, this CMV UL54 mutation occurred in the absence of a UL97 mutation. Additionally, new UL54 variants were observed. Thus, emergence of CMV UL54 mutations in the absence of UL97 mutations is a rare but possible event that is not necessarily associated with detrimental clinical outcome in solid organ transplant recipients. J. Med. Virol. 77:425–429, 2005.

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