Research Article: Cytomegalovirus viraemia is associated with poor growth and T-cell activation with an increased burden in HIV-exposed uninfected infants

Date Published: August 24, 2017

Publisher: Lippincott Williams & Wilkins

Author(s): Miguel A. Garcia-Knight, Eunice Nduati, Amin S. Hassan, Irene Nkumama, Timothy J. Etyang, Naseem J. Hajj, Faith Gambo, Denis Odera, James A. Berkley, Sarah L. Rowland-Jones, Britta Urban.


Factors associated with poor health in HIV-exposed-uninfected (HEU) infants are poorly defined. We describe the prevalence and correlates of cytomegalovirus (CMV) viraemia in HEU and HIV-unexposed-uninfected (HUU) infants, and quantify associations with anthropometric, haematological, and immunological outcomes.

Cross-sectional, including HEU and HUU infants from rural coastal Kenya.

Infants aged 2–8 months were studied. The primary outcome was CMV viraemia and viral load, determined by quantitative PCR. Correlates were tested by logistic and linear regression; coefficients were used to describe associations between CMV viraemia and clinical/immunological parameters.

In total, 42 of 65 (64.6%) infants had CMV viraemia [median viral load, 3.0 (interquartile ranges: 2.7–3.5) log10 IU/ml]. Compared to community controls, HEU infants had six-fold increased odds of being viraemic (adjusted odds ratio 5.95 [95% confidence interval: 1.82–19.36], P = 0.003). Age, but not HEU/HUU status, was a strong correlate of CMV viral load (coefficient = −0.15, P = 0.009). CMV viral load associated negatively with weight-for-age (WAZ) Z-score (coefficient =  −1.06, P = 0.008) and head circumference-for-age Z-score (coefficient =  −1.47, P = 0.012) and positively with CD8+ T-cell coexpression of CD38/human leucocyte antigen DR (coefficient = 15.05, P = 0.003).

The odds of having CMV viraemia was six-fold greater in HEU than HUU infants when adjusted for age. CMV viral load was associated with adverse growth and heightened CD8+ T-cell immune activation. Longitudinal assessments of the clinical effects of primary CMV infection and associated immunomodulation in early life in HEU and HUU populations are warranted.

Partial Text

Successful prevention of mother-to-child transmission (PMTCT) of HIV-1 strategies have given rise to an increased number of HIV-exposed uninfected (HEU) infants over the past decade [1]. Despite these gains, higher morbidity and mortality is observed in HEU infants compared with infants born to HIV-uninfected mothers (referred to as HIV-unexposed uninfected [HUU]) [2–5]. Defining the mechanisms of poor health in this population is an increasing public health priority.

Much attention has been paid to the impact of HIV and ART exposure on adverse delivery outcomes [35,36], metabolic [37,38] and haematological [39,40] abnormalities, and immunological alterations [41,17] in HEU infants. The impact of maternal coinfections on HEU infant health is relatively underexplored and may directly impact some of the outcomes mentioned above. We assessed the burden and possible risk factors for systemic CMV replication in infancy in HEU and HUU infants and explored associations between CMV viraemia and anthropometric, haematological, and immunological outcomes. Our main findings were: a six-fold increased odds ratio of CMV viraemia in HEU infants compared to HUU infants; a strong negative association between CMV viral load and infant age; significant negative associations between CMV viral load and infant WAZ and head circumference-for-age Z-scores; and a significant positive association between CMV viral load and CD8+ T cell activation.

We primarily thank the infants and mothers who participated in the study. We also thank the staff at the Comprehensive Care and Research Clinic namely, Anne Njogu, Margaret Lozi, Salma Said, Jefwa Kithunga, and Conny Kadenge. Finally, we thank Greg Fegan for guidance with statistical considerations. This manuscript was submitted for publication with the permission from the Director of the Kenya Medical Research Institute (KEMRI).




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