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Background: In resource-rich settings, the rate of mother-to-child transmission of human immunodeficiency virus (HIV) has dramatically decreased by virtue of a combination of preventive strategies during the last two decades. Case Presentation: We present a case of progressive developmental milestone loss in a toddler with previously unknown congenitally acquired human immunodeficiency virus (HIV) infection, complicated by an Epstein-Barr virus (EBV) coinfection. Conclusion: Our report underscores the differential diagnosis between HIV encephalopathy and EBV encephalitis and the vertical transmission of the HIV infection, which constitutes an alarming issue in terms of public health.