Unexpected Cytomegalovirus (CMV) Replication Kinetics in CMV Donor-Seropositive, Recipient-Seronegative Liver Transplant Recipients Receiving Preemptive Antiviral Therapy

• Published in: The Journal of infectious diseases 2022-02, Vol.225 (3), p.436-442
• Main Authors: Singh, Nina, Winston, Drew J, Razonable, Raymund R, Marshall Lyon, G, Silveira, Fernanda P, Wagener, Marilyn M, Limaye, Ajit P
• Format: Article
• Language: English
• Subjects: Antiviral agents; Antiviral Agents - therapeutic use; Antiviral drugs; Cytomegalovirus; Cytomegalovirus Infections - drug therapy; Cytomegalovirus Infections - prevention & control; DNA-directed DNA polymerase; Ganciclovir - therapeutic use; Humans; Kinetics; Liver Transplantation; Liver transplants; Major and Brief Reports; Patients; Polymerase chain reaction; Population studies; Transplant Recipients; Viremia; Viremia - drug therapy
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiab132

Abstract Background Detailed cytomegalovirus (CMV) kinetics in donor CMV-seropositive, recipient CMV-seronegative (D+/R–) transplant recipients receiving preemptive therapy (PET) have not been fully defined. Methods The study population consisted of the PET arm of a randomized CMV prevention trial in D+/R– liver transplant recipients. CMV DNA polymerase chain reaction (PCR) assays were performed weekly for 100 days using a sensitive assay. Viral load and clinical parameters were compared for patients with or without high-level increase (defined as higher than the group median log10 increase in viral load from baseline after PET initiation). Results Among 79 patients, 93.6% (74/79) developed an increase from baseline viral loads of median 120 IU/mL to 3350 IU/mL; 25.7% (19/74) of the patients had peak levels >10 000 IU/mL. None of the patients with rise in viral load underwent testing for CMV resistance, and viremia resolved with PET with valganciclovir. Patients with high-level increase in viral load had a significantly lower rate of recurrent viremia than those without such increase (16/40 [40%] vs 28/39 [71.8%], respectively; P = .004). Conclusions A majority of D+/R– recipients had a marked increase in viral load after initiation of PET before resolution of viremia. This phenomenon is associated with lower rates of subsequent recurrent viremia and does not necessarily imply antiviral resistance. A significant increase in viral load after preemptive therapy occurs in a majority of D+/R– liver transplant recipients and is associated with lower risk of recurrent viremia.