Photo Credit: Mohammed Haneefa Nizamudeen

The following is a summary of “Cytomegalovirus antiviral resistance among participants in the phase 3 trial of letermovir vs valganciclovir prophylaxis in kidney transplant recipients,” published in the June 2024 issue of Infectious Disease by Strizki et al.

Researchers conducted a retrospective study of a phase 3 trial to assess the efficacy of letermovir compared to valganciclovir for CMV disease prophylaxis in CMV-seronegative (R-) kidney transplant recipients (KTRs) who received a kidney from a CMV-seropositive donor (D+). Genotypic antiviral resistance and CMV glycoprotein B (gB) genotype have been reported.

They sequenced plasma samples containing detectable CMV DNA to identify known letermovir and valganciclovir resistance-associated amino acid substitutions (RASs) encoded by CMV gene regions (UL51, UL56, UL89, UL54, UL97) and to determine the prevalence of gB (UL55) genotypes (gB1-gB5).

The results showed 292 participants in the letermovir group, 84 out of 297 in the valganciclovir group, and 93 had evaluable data for ≥1 gene target. Letermovir RASs weren’t found in those who received letermovir prophylaxis, but 3 had valganciclovir RASs (pUL97). In the valganciclovir group, 12 participants had valganciclovir RASs (pUL54, pUL97), and 1 who didn’t receive letermovir during the trial also had letermovir RASs (pUL56). Almost all participants responded to valganciclovir treatment regardless of breakthrough CMV DNAemia or frequency of RASs. The most frequent genotype across all participants and subgroups was gB1.

Investigators found no evidence of letermovir RASs in the letermovir group, suggesting a low risk of resistance developing during letermovir prophylaxis for CMV D+,  KTRs who are CMV R-.

Source: academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiae287/7690303