Sharma and colleagues (2021) demonstrated that spliced HIV RNA appears in the cerebrospinal fluid of CD4 T cells during the earliest stages of infection in simian-human immunodeficiency virus (SHIV)-infected rhesus macaques, resembling the observation in human acute HIV infection, whereby peak plasma SHIV RNA occurs two weeks post-infection, followed by a gentle decrease [9]. Here, CD4 is linked to infection.