Cytomegalovirus Acquisition and Inflammation in Human Immunodeficiency Virus-Exposed Uninfected Zimbabwean Infants

Abstract

Cytomegalovirus (CMV) acquisition and inflammation were evaluated in 231 human immunodeficiency virus (HIV)-exposed uninfected (HEU) and 100 HIV-unexposed Zimbabwean infants aged 6 weeks. The HEU and HIV-unexposed infants had a similarly high prevalence of CMV (81.4% vs 74.0%, respectively; P = .14), but HEU infants had higher CMV loads (P = .005) and >2-fold higher C-reactive protein (CRP) concentrations (P < .0001). The CMV-positive HEU infants had higher CRP than the CMV-negative HEU infants; this association disappeared after adjusting for maternal HIV load. Overall, CMV acquisition is high in early life, but HEU infants have higher CMV loads and a proinflammatory milieu, which may be driven partly by maternal HIV viremia.

Keywords: HIV-exposed uninfected infants; cytomegalovirus; immune activation; inflammation; Africa.

Figure 1.

Relationship between cytomegalovirus (CMV), C-reactive protein (CRP), and human immunodeficiency virus (HIV) exposure status. A, Prevalence of CMV DNAemia at 6 weeks of age in HIV-unexposed and HIV-exposed uninfected infants. Proportions in each group compared using Fisher’s exact test. B, CMV loads in HIV-unexposed and HIV-exposed uninfected infants. Horizontal line at median. Median CMV viral loads compared between HIV-exposed and HIV-unexposed infant groups using Mann–Whitney test. Limit of quantification of CMV load: 45 copies/mL; CMV-positive samples with viral loads below the limit of quantification were arbitrarily assigned CMV load values of 40 copies/mL. C, C-reactive protein in infants with and without CMV acquisition by 6 weeks of age, stratified by HIV exposure category. White circles: CMV-negative HIV-unexposed infants; white triangles: CMV-positive HIV-unexposed infants; black squares: CMV-negative HIV-exposed uninfected infants; black diamonds: CMV-positive HIV-exposed uninfected infants. Horizontal line at median. All comparisons undertaken using Mann–Whitney tests. D, Maternal HIV disease severity in HEU infants with and without CMV acquisition by 6 weeks of age. Left y-axis: maternal HIV load; right y-axis: maternal CD4 count. Black squares: maternal viral load in CMV-negative infants; black circles: maternal viral load in CMV-positive infants; black downwards-pointing triangles: maternal CD4 count in CMV-negative infants; black upwards-pointing triangles: maternal CD4 count in CMV-positive infants. HIV-exposed uninfected infants only. Horizontal line at median. All comparisons undertaken using Mann–Whitney tests.