We present the case of a young boy who was born to a human immunodeficiency virus (HIV)-positive mother and originally found to be uninfected. Evidence-based guidelines were followed regarding the mother's prenatal and infant's postnatal care, including the avoidance of breast milk. HIV DNA polymerase chain reaction qualitative tests were obtained at birth, 6 weeks and 4 months, and were all negative. He also received 6 weeks of prophylactic zidovudine. Despite these measures, his health began to decline at 17 months of age and antibody and serology tests performed at this time confirmed HIV infection. Guidelines no longer recommend routine antibody testing at 18 months of age to confirm the absence of infection in exposed infants with a record of negative virology in the first year of life. Based on this case and others we propose that this test be added back to the national guidelines for the early detection and prompt treatment of HIV infection in infants born to HIV-positive mothers.