Current combination antiretroviral therapies (cART) are unable to eradicate HIV-1 virus from infected individuals， because of the establishment of proviral latency in long-lived cellular reservoirs. The "shock and kill" approach aims to reactivate viral replication from the latent state ("shock") using latency reversing agents (LRAs)， followed by the elimination of reactivated virus-producing cells ("kill") by specific therapeutics. The NF-κB RelA/p50 heterodimer has been characterized as an essential component of reactivation of the latent HIV-1 long terminal repeat. Nevertheless， prolonged NF-κB activation contributes to the development of various autoimmune， inflammatory and malignant disorders. In the present study we established a cellular model of HIV-1 latency in JLat CD4 T cells that stably expressed the NF-κB super-repressor IκB-α 2NΔ4， and demonstrate that conventional treatments， with Bryostatin-1 and Hexamethylenebisacetammide (HMBA) or Ionomycin， synergistically reactivated HIV-1 from latency， even under conditions where NF-κB activation was repressed. Using specific calcineurin phosphatase， p38， and MEK1/MEK2 kinase inhibitors， or specific shRNAs， c-Jun was identified as an essential factor binding to the LTR enhancer kB sites and mediating the combined synergistic reactivation effect. Furthermore， acetyl salicylic acid (ASA)， a potent inhibitor of the NF-κB activator kinase IKK-β， did not significantly diminish reactivation in a primary CD4 T central memory (Tcm) cell latency model. The present work demonstrates that the "shock" phase of the "shock and kill" approach to reverse HIV-1 latency may be achieved in the absence of NF-κB， with the potential to avoid unwanted autoimmune and or inflammation related side effects associated with latency reversing strategies.The "shock and kill" approach consists in the reactivation of HIV-1 replication from latency using latency reversing agents (LRAs)， followed by the elimination of reactivated virus-producing cells. The cellular transcription factor NF-κB is considered a master mediator of HIV-1 escape from latency induced by LRAs. Nevertheless， a systemic activation of NF-κB in HIV-1 patients， resulting from the combined administration of different LRAs， could represent a potential risk especially in the case of a prolonged treatment. We here demonstrate that conventional treatments with Bryostatin-1 and Hexamethylenebisacetammide (HMBA) or Ionomycin synergistically reactivated HIV-1 from latency， even under conditions where NF-κB activation was repressed. Our study provides a molecular proof of concept for the use of anti-inflammatory drugs， like aspirin， capable of inhibiting NF-κB in patients under cART during the "shock and kill" approach， to avoid potential autoimmune and inflammatory disorders that can be elicited by combinations of LRAs.