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)
Summary
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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