The natural history of Epstein-Barr virus (EBV) infection in the setting of human immunodeficiency virus type 1 (HIV-1) disease was studied in 600 liveborn infants born to 555 mothers infected with HIV-1 in a 6-year, prospective, multicenter cohort study. Acquisition of EBV infection was identified by oropharyngeal shedding or seroconversion from samples obtained every 6 months from all patients. HIV-1-infected and HIV-1-uninfected children were compared for the age of onset and the subsequent frequency of oropharyngeal EBV shedding, EBV serologic profiles, and the effect of EBV infection on clinical symptoms and laboratory measurements. EBV infection occurred at a high rate in early childhood in both HIV-1-infected and HIV-1-uninfected children born to HIV-1-infected mothers. Approximately 75% of children in both groups were infected with EBV by the age of 30 months. HIV-1-infected children also infected with EBV had a higher probability of oropharyngeal EBV shedding (47% ±5% overall) compared to HIV-1-uninfected children (28% ±2% overall) who were infected with EBV. The probability of oropharyngeal EBV shedding in HIV-1-infected children decreased with longer time from initial EBV infection and was similar to that of HIV-1-uninfected children by 36-months after EBV seroconversion. Neither acute or active EBV infection had a discernible effect on CD4 cell count, percent CD4, or total immunoglobulin levels. HIV-1-infected children with EBV infection had higher CD8 cell counts compared to HIV-1-uninfected children without EBV infection. HIV-1 but not EBV infection was associated with lymphadenopathy, hepatomegaly, and splenomegaly. HIV-1-infected children identified with rapid HIV-1 disease progression were more likely to shed EBV(68.1%) than non-rapid progressors (40.1%) (overall P=0.004) or HIV-1-uninfected children who were also infected with EBV(32.6%). Children with rapid HIV-1 disease progression also demonstrated impaired humoral immune response to EBV infection. We conclude that EBV infection is ubiquitous in children born to HIV-1-infected mothers, and that HIV-1-infected children demonstrate increased EBVshedding, especially those children with rapid HIV-1 disease progression who also demonstrate a poorer antibody response to EBV infection.
