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Cytomegalovirus (CMV) is a frequent opportunistic infection in human immunodeficiency virus type 1 (HIV-1)-infected children. The interactions of CMV and HIV-1 in coinfected children are not well-characterized.To evaluate the prevalence of asymptomatic CMV infection and symptomatic CMV disease and to assess the influence of CMV on clinical and laboratory markers of HIV disease progression in CMV-coinfected children.Serial urine CMV cultures were performed on 500 children (131 HIV-1-infected (HIV+), 129 seroreverters born to HIV-infected mothers, and 240 HIV-uninfected (HIV-)). The clinical, immunologic and virologic data of 131 HIV+ children were analyzed.CMV was recovered in 40 of 131 HIV+ (31%), 22 of 129 seroreverters (17%) and 30 of 240 HIV- (13%) children. Of the 40 HIV+ children with CMV coinfection, 7 developed symptomatic CMV disease (17.5%) including chorioretinitis (3), colitis (2) and pneumonitis (2). The HIV+ children with symptomatic CMV disease had significantly lower mean CD4+ T lymphocyte proportions (17% vs. 26%; age-adjusted P = 0.013) and greater HIV p24 antigen concentrations (329 pg/ml vs. 57 pg/ml; age-adjusted P = 0.13) than HIV+ children with asymptomatic CMV infection. In a subset of children coinfected with CMV before 6 months of age (n = 11), 5 (45%) developed symptomatic CMV disease, and 4 of these 5 children died within 10 months of diagnosis of CMV disease. At the time of the first positive CMV culture in these children, mean CD4+ T lymphocyte proportions did not differ according to the presence or absence of CMV-related symptoms (symptomatic CMV+, 21% vs. asymptomatic CMV = 38%; P = 0.14). In HIV+ children with symptomatic CMV disease, p24 antigen concentrations were greater than in those with asymptomatic CMV infection (461 vs. 190 pg/ml, P = 0.06).Symptomatic CMV disease occurred in young CMV-coinfected children with low CD4+ lymphocytes and elevated HIV p24 antigen concentrations. Whether progressive immunodeficiency allows the emergence of CMV disease or CMV infection causes more rapidly progressive HIV-1 disease or whther there is a more complex relationship remains to be determined.