A previously healthy 26-year-old man presented to the emergency department with a 5-day history of an asymptomatic rash, sore throat, fevers, chills, and malaise. On physical examination, scattered, erythematous papules and macules could be seen across the upper chest and anterior neck (Panel A). In the mouth, palatal petechiae, buccal mucosal ulcerations, and pharyngeal erythema were observed (Panel B). There was no palpable lymphadenopathy. Laboratory testing showed leukopenia, lymphopenia, mild thrombocytopenia, and an elevated C-reactive protein level. Tests for several respiratory viral pathogens, EpsteinβBarr virus, measles, rubella, and syphilis were negative. A rapid antibody test for human immunodeficiency virus (HIV) was negative. However, a subsequent fourth-generation combination HIV antigen and antibody test was positive, and the HIV viral load was greater than 10 million copies per milliliter (reference value, undetectable). A diagnosis of acute HIV infection was made. The patient reported having had condomless sex with a new partner 2 weeks before presentation. In acute HIV infection, HIV antibodies do not form until several weeks after infection, whereas HIV viremia and the p24 antigen are detectable much earlier. Antiretroviral therapy was started, and the patientβs symptoms rapidly abated.