Program Schedule

Co-Reactivation of Human Herpesvirus 6 (HHV-6) and Cytomegalovirus (CMV) is Associated with Worse Clinical Outcome in Critically Ill Immunocompetent Adults

Session: Oral Abstract Session: Viral Infections: Clinical Trials and Pathogenesis
Friday, October 10, 2014: 2:45 PM
Room: The Pennsylvania Convention Center: 105-AB

Background: A systematic assessment of human herpesvirus 6 (HHV-6) reactivation and association with adverse outcomes in immunocompetent adults with critical illness has not been reported.

Methods: We assessed HHV-6 and CMV viremia by twice weekly plasma PCR in a prospective cohort of 115 CMV seropositive immunocompetent adults admitted to 4 types of intensive care units (ICU) (medical, burn, trauma, cardiac). The association of HHV-6 and CMV reactivation with death or continued hospitalization by day 30 (primary endpoint) was assessed by logistic regression.

Results: The primary endpoint developed in 44 (38%) of 115 patients. HHV-6 viremia occurred in 27 patients (23%) at a median of 10 days (range, 0 to 75 days) (Table 1, Fig. 1). No patients had findings consistent with chromosomally integrated HHV-6. Most patients with HHV-6 reactivation also reactivated CMV (70%); 49% with CMV also reactivated HHV-6. There was no significant difference in timing of viral reactivation. Severity of illness measured by APACHE II score was not associated with either HHV-6 or CMV reactivation. In multivariable models adjusting for baseline factors (ICU, mechanical ventilation), HHV-6 (adjusted odds ratio [aOR], 3.5; 95% CI, 1.2-10.3; p=0.03) and CMV (aOR, 3.4; 95% CI, 1.3-8.9; p=0.01) viremia each were independently associated with the primary endpoint. Co-reactivation of both HHV-6 and CMV was even more strongly associated with the primary endpoint than reactivation of either virus alone or no viral reactivation (aOR, 7.5; 95% CI, 1.9-29.8; p=0.004).

Conclusion: Co-reactivation of HHV-6 and CMV in ICU patients is strongly and independently associated with worse outcome. Future studies should define the mechanism(s) underlying this association and whether prevention of viral reactivation improves clinical outcome.


Table 1.

                                                                      All ICUs, n = 115




Viremia at any level, n (%)

27 (23)

39 (34)

Viremia >1000 copies/ml, n (%)

6 (5)

24 (21)

Days to viremia, median (range)

10 (0-75)

12 (3-57)

Reactivation by ICU, n (%)*




8 (40)

11 (55)


8 (20)

15 (38)


8 (20)

10 (25)


3 (15)

3 (15)

*Number of reactivation events per ICU

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Joshua Hill, MD1,2, Paula Roa, PharmD3, Katharine Kirby, MSc4, Meei-Li Huang, PhD5,6, Tracy Santo, BSc5, Keith Jerome, MD, PhD5,6, Michael Boeckh, MD1,6 and Ajit Limaye, MD, FIDSA1,5, (1)Department of Medicine, University of Washington, Seattle, WA, (2)Fred Hutchinson Cancer Research Center, Seattle, WA, (3)Department of Microbiology and Infectious Diseases, Hospital Gregorio Maranon, Madrid, Spain, (4)Department of Medicine, University of California San Francisco, San Francisco, CA, (5)Department of Laboratory Medicine, University of Washington, Seattle, WA, (6)Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA


J. Hill, None

P. Roa, None

K. Kirby, None

M. L. Huang, None

T. Santo, None

K. Jerome, None

M. Boeckh, Chimerix, Inc.: Consultant, Research support
Genentech/Roche: Consultant, Research support
Gilead: Consultant, Research support
Clinigen: Consultant, Research support

A. Limaye, viropharma: Consultant, Research support
genentech: Consultant, Research support
Astellas: Consultant, Research support

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