Coreactivation of Human Herpesvirus 6 and Cytomegalovirus Is Associated With Worse Clinical Outcome in Critically Ill Adults.

OBJECTIVES:Human herpesvirus 6 is associated with a variety of complications in immunocompromised patients, but no studies have systematically and comprehensively assessed the impact of human herpesvirus 6 reactivation, and its interaction with cytomegalovirus, in ICU patients. DESIGN:We prospectively assessed human herpesvirus 6 and cytomegalovirus viremia by twice-weekly plasma polymerase chain reaction in a longitudinal cohort study of 115 adult, immunocompetent ICU patients. The association of human herpesvirus 6 and cytomegalovirus reactivation with death or continued hospitalization by day 30 (primary endpoint) was assessed by multivariable logistic regression analyses. SETTING:This study was performed in trauma, medical, surgical, and cardiac ICUs at two separate hospitals of a large tertiary care academic medical center. PATIENTS:A total of 115 cytomegalovirus seropositive, immunocompetent adults with critical illness were enrolled in this study. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Human herpesvirus 6 viremia occurred in 23% of patients at a median of 10 days. Human herpesvirus 6B was the species detected in eight samples available for testing. Most patients with human herpesvirus 6 reactivation also reactivated cytomegalovirus (70%). Severity of illness was not associated with viral reactivation. Mechanical ventilation, burn ICU, major infection, human herpesvirus 6 reactivation, and cytomegalovirus reactivation were associated with the primary endpoint in unadjusted analyses. In a multivariable model adjusting for mechanical ventilation and ICU type, only coreactivation of human herpesvirus 6 and cytomegalovirus was significantly associated with the primary endpoint (adjusted odds ratio, 7.5; 95% CI, 1.9-29.9; p = 0.005) compared to patients with only human herpesvirus 6, only cytomegalovirus, or no viral reactivation. CONCLUSIONS:Coreactivation of both human herpesvirus 6 and cytomegalovirus in ICU patients is associated with worse outcome than reactivation of either virus alone. Future studies should define the underlying mechanism(s) and determine whether prevention or treatment of viral reactivation improves clinical outcome.