AbstractA cure for human immunodeficiency virus type‐1 (HIV‐1) has been hampered by the limitation of current combination antiretroviral therapy (cART) to address the latent reservoirs in HIV‐1 patients. One strategy proposed to eradicate these reservoirs is the “shock and kill” approach, where latency‐reversing agents (LRAs) are used to reactivate and promote viral cell death and/or immune killing of reactivated cells. Here, we report that curaxin CBL0137, an antitumor compound, can potentiate tumor necrosis factor‐α‐mediated reactivation of latently infected HIV‐1cell lines. Additionally, the single use of CBL0137 is sufficient to reactivate HIV‐1 latent reservoirs in peripheral mononuclear cells (PBMCs) isolated from HIV‐1 positive, cART‐treated, aviremic patients. Thus, CBL0137 possesses capabilities as a LRA and could be considered for the “shock and kill” approach.