CMV (Cytomegalovirus) is a ubiquitous human herpes virus that causes adverse clinical outcomes in immunocompromised individuals, such as hematopoietic cell transplant (HCT) and solid organ transplant (SOT) recipients and those infected with human immunodeficiency virus (HIV). CMV infection is the most frequent viral complication after HCT, and current strategies using either preemptive or prophylactic antivirals have not eliminated CMV complications. Up to 50% of HCT recipients with CMV pneumonia still die even with aggressive treatment.
Our research in immunocompromised patients takes a multifaceted approach to identifying epidemiologic risk factors for CMV infection, defining the viral kinetics, and improving prevention, diagnosis and treatment strategies. By better understanding the kinetics of the reconstitution of CMV-specific immune function following transplantation, we seek to define the components of protective cellular and humoral immunity by testing multifunctionality and neutralizing Abs directed against the pentameric complex. We are also working to elucidate the mode of CMV transmission in HCT in seropositive donor/ seronegative recipient pairings.
Reactivation of CMV in apparently immunocompetent patients with critical illness due to a broad range of causes has been documented in multiple prior studies using a variety of virologic techniques. In addition to CMV reactivation in sepsis, CMV reactivation has also been demonstrated specifically in lung and blood of patients with acute lung injury (ALI). CMV reactivation could provide a mechanistic link between ALI and persistent dysregulated inflammation, and provides a novel target for intervention to reduce the morbidity and mortality of sepsis-associated ALI and its complications in adults. A recently completed phase 2 clinical trial demonstrated that antiviral prophylaxis can prevent CMV reactivation and may lead to shorter durations of mechanical ventilation. A phase 3 clinical trial is being designed.