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

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

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

Methods: 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.

Results: 42/65 (64.6%) infants had CMV viraemia (median viral load, 3.0 [IQR: 2.7-3.5] log10 IU/mL). Compared to community controls, HEU infants had 6-fold increased odds of being viraemic (adjusted OR 5.95 [95% CI: 1.82-19.36], P=0.003). Age, but not HEU/HUU status, was a strong correlate of CMV viral load (coeff = -0.15, P = 0.009). CMV viral load associated negatively with weight-for-age z-score (coeff. = -1.06, P = 0.008) and head circumference-for-age z-score (coeff. = -1.47, P = 0.012) and positively with CD8 T cell co-expression of CD38/HLADR (coeff. = 15.05, P = 0.003).

Conclusions: 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.