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Palpable disappointment accompanied the news last month of a child (the “Mississippi baby”) who was thought to be cured of HIV-1 infection by early antiretroviral treatment, but suddenly had detectable virus in the blood 2 years after the treatment was stopped. This setback followed the report of similar delayed viral rebounds 3 to 8 months after antiretroviral treatment was ended in two HIV-1–infected adults who had received bone marrow transplants (1). These findings have been viewed as a blow to HIV-1 eradication efforts. Although disappointing, the late rebounds are of enormous scientific importance. They reaffirm the concept that HIV-1 can persist by establishing latent infection and point to this challenge as the major hurdle in achieving a cure for HIV-1 infection.