Letermovir for Primary Cytomegalovirus Prophylaxis in Pulmonary Fibrosis Lung

We have previously shown short telomere pulmonary fibrosis lung transplant recipients (STL IPF-LTRs) have impaired CMV-specific immunity and increased susceptibility to CMV complications post-transplant. STL IPF-LTRs are also susceptible to cytopenias exacerbated by the standard CMV prophylaxis medication, Valganciclovir. We investigated Letermovir as an alternative primary CMV prophylaxis and its impact on CMV viremia in a cohort of 24 IPF-LTRs with 14/24 (58%) CMV R+, 10/24 (42%) CMV D+/R- and 67% (16/24) STL. Only 1 patient demonstrated CMV DNAemia during Letermovir prophylaxis, while post-Letermovir CMV DNAemia was more common among CMV D+/R- patients. CMV-specific CD8+ T-cell responses were preserved in R+ patients, including STL IPF-LTRs. The absence of CMV-specific CD8+ T-cell responses in high-risk D+/R- LTRs at the end of prophylaxis was consistent with viral suppression during therapy. We found that Letermovir use for primary CMV prophylaxis was safe, efficacious, and highly effective for viral suppression and prevention of primary infection post-lung transplant.