Abstract

Objective: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.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: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).Conclusion: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.

Highlights

  • 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]

  • No significant baseline differences between HEU and HUU infants were observed with regards to age and sex, though HEU infants had increased lymphocyte counts (P 1⁄4 0.04)

  • Cytomegalovirus viral load is strongly associated with infant age Median viral load among all 42 CMV viraemic infants was 3.0 (IQR: 2.6–3.5) log10 IU/ml: 3.1 [IQR: 2.7–3.5] log10 IU/ml among HEU infants and 2.7 (IQR: 2.4–3.2) log10 IU/ml among HUU infants (P 1⁄4 0.161)

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Summary

Introduction

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]) [2,3,4,5]. A relatively unexplored influence is exposure to maternal coinfections. Cytomegalovirus (CMV) is a common maternal coinfection with high seroprevalence, especially in countries that have high HIV-1 prevalence (80–100% in pregnant women) [10,11]

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