Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

INTRODUCTION: Immunocompetent patients can reactivate latent cytomegalovirus (CMV) during critical illness and reactivation is associated with significantly worse outcomes. Prior to clinical trials in humans to prove causality, we sought to determine an optimal antiviral treatment strategy. METHODS: Mice latently infected with murine CMV (MCMV) received a septic reactivation trigger and were randomized to receive one of four ganciclovir regimens or saline. Lungs were evaluated for viral transcriptional reactivation and fibrosis after each regimen. Influences of ganciclovir on early sepsis-induced pulmonary inflammation and T-cell activation were studied after sepsis induction. RESULTS: All ganciclovir regimens reduced measurable MCMV transcriptional reactivation, and 10mg/day for 7 or 21 days was most effective. Lower dose (5mg/kg/day) or delayed therapy was associated with significant breakthrough reactivation. Higher doses of ganciclovir given early were associated with the lowest incidence of pulmonary fibrosis, and delay of therapy for 1 week was associated with significantly worse pulmonary fibrosis. Although bacterial sepsis induced activation of MCMV-specific pulmonary T-cells, this activation was not influenced by ganciclovir. CONCLUSION: These results suggest that antiviral treatment trials in humans should use 10mg/kg/day ganciclovir administered as early as possible in at-risk patients to minimize reactivation events and associated pulmonary injury.

Original publication

DOI

10.1016/j.antiviral.2009.12.004

Type

Journal article

Journal

Antiviral Res

Publication Date

03/2010

Volume

85

Pages

496 - 503

Keywords

Animals, Antiviral Agents, Cytomegalovirus Infections, Disease Models, Animal, Female, Ganciclovir, Humans, Lung, Mice, Mice, Inbred BALB C, Muromegalovirus, Random Allocation, Sepsis, Virus Activation