When combination antiretroviral therapy (ART) was first administered to HIV-infected individuals in the 1990s, patient viral loads declined so rapidly that it seemed a cure could be achieved within 2-3 y of therapy (1). However, the presence of a long-lived reservoir of latently infected CD4+ memory T cells (2) diminished these hopes. When ART was interrupted in patients, even after many years, viremia rapidly rebounded from the latent reservoir and the estimates indicated that it would take many decades of suppressive therapy for the reservoir to dissipate. To achieve an HIV cure, the latent reservoir would need to be actively emptied while the resulting virus was destroyed using antiretroviral drugs. The strategy became known as “activate-and-kill” (Fig. 1A), and a vigorous research campaign ensued to identify agents capable of reactivating latent HIV.
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