Cytomegalovirus Viremia Predicts Postdischarge Mortality in Kenyan HIV-Exposed Uninfected Children

Author:

Pavlinac Patricia B12ORCID,Singa Benson34,Huang Meei-Li56,Shrestha Lasata6,Li Vanessa1,Atlas Hannah E1,Diakhate Mame Mareme1,Brander Rebecca1,Meshak Liru7,Bogonko George8,Tickell Kirkby D14,McGrath Christine J14,Machuara Irine M3,Ounga Derrick O3,Berkley James A4910,Richardson Barbra A111,John-Stewart Grace121213ORCID,Walson Judd L1241213,Slyker Jennifer12

Affiliation:

1. Department of Global Health, University of Washington , Seattle, Washington , USA

2. Department of Epidemiology, University of Washington , Seattle, Washington , USA

3. Kenya Medical Research Institute , Nairobi , Kenya

4. Childhood Acute Illness and Nutrition Network , Nairobi , Kenya

5. Fred Hutchinson Cancer Research Center , Seattle, Washington , USA

6. Department of Laboratory Medicine, University of Washington , Seattle, Washington , USA

7. Homa Bay Teaching and Referral Hospital , Homa Bay , Kenya

8. Kisii Teaching and Referral Hospital , Kisii , Kenya

9. Kenya Medical Research Institute-Wellcome Trust Research Programme , Kilifi , Kenya

10. Center for Tropical Medicine and Global Health, University of Oxford , Oxford , United Kingdom

11. Department of Biostatistics, University of Washington , Seattle, Washington , USA

12. Department of Medicine, Allergy, and Infectious Disease, University of Washington , Seattle, Washington , USA

13. Department of Pediatrics, University of Washington , Seattle, Washington , USA

Abstract

Abstract Background Cytomegalovirus (CMV) viremia is associated with mortality in severely ill immunocompetent adults and hospitalized children with HIV (CWH). We measured CMV viremia in HIV-exposed and -unexposed Kenyan children aged 1–59 months discharged from hospital and determined its relationship with postdischarge mortality. Methods CMV DNA levels were measured in plasma from 1024 children (97 of which were HIV exposed uninfected [HEU], and 15 CWH). Poisson and Cox proportional hazards regression models were used to identify correlates of CMV viremia ≥ 1000 IU/mL 
and estimate associations with 6-month mortality, respectively. Results CMV viremia was detected in 31% of children, with levels ≥ 1000 IU/mL in 5.8%. HIV infection, age < 2 years, breastfeeding, and midupper arm circumference < 12.5 cm were associated with CMV viremia ≥ 1000 IU/mL. Among HEU children, CMV ≥ 1000 IU/mL (hazard ratio [HR] = 32.0; 95% confidence interval [CI], 2.9–354.0; P = .005) and each 1-log increase in CMV viral load (HR = 5.04; 95% CI, 1.7–14.6; P = .003) were associated with increased risk of mortality. CMV viremia was not significantly associated with mortality in HIV-unexposed children. Conclusions CMV levels at hospital postdischarge predict increased risk of 6-month mortality in Kenyan HEU children. CMV suppression may be a novel target to reduce mortality in HEU children. Clinical Trial Registration NCT02414399.

Funder

Eunice Kennedy Shriver National Institute of Child Health and Human Development

National Institutes of Health

University of Washington Center for AIDS Research

University of Washington Global Center for Integrated Health of Women, Adolescents, and Children

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

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