AbstractWU polyomavirus (WUPyV), a new member of the genus wukipolyomavirus in the family Polyomaviridae, has been detected in serum and tissues of individuals infected with HIV. However, the epidemiology of WUPyV among children exposed perinatally to HIV‐1 is unknown. To investigate the epidemiology of WUPyV in children exposed to and infected perinatally with HIV, serum samples from 150 children exposed to HIV and 114 children infected with HIV were screened for IgG antibodies to WUPyV. A subset was screened for IgM antibodies to WUPyV. Both antibody detection assays were performed using a recombinant WUPyV VP1‐based ELISA. The overall seroprevalence of WUPyV IgG was 76.3% in children infected with HIV and 62% in children exposed perinatally to HIV. In the group of children infected with HIV, the prevalence of WUPyV IgG antibody reached its peak in 2–3 year olds (90.9%). In children 0–5 months of age, IgG seroprevalence was lower in those children exposed to HIV compared to children infected with HIV (43.1% vs.75%, P = 0.047). However, the seroprevalence of WUPyV IgM antibody was higher in children exposed to HIV compared to infants infected with HIV (27.4% vs. 8.3%, P = 0.044). WUPyV infection is acquired in early childhood in the majority of children born to mothers infected with HIV. The implication of this infection and the specific clinical syndrome that it produces, if any, remain to be defined. J. Med. Virol. 84:188–193, 2012. © 2011 Wiley Periodicals, Inc.