My current research focus is on HIV-1 latency reversal and elimination. Combinatorial antiretroviral therapy (cART) has transformed HIV infection from a death sentence to a controllable chronic disease but cannot eliminate the virus. Latent HIV-1 reservoirs are the major obstacles to cure HIV-1 infection. “Shock and kill” strategy, which reactivates latent HIV-1 from its reservoirs and renders the reservoir cells with reactivated HIV-1 to the immune system, appears to be a promising approach to eliminate latent HIV-1. Previously, we have engineered exosomal Tat to reactivate latent HIV-1 from the reservoir of resting CD4+ T cells (Tang et al. JCI Insight. 2018; 3(7): e95676.). We further demonstrated that exosomal Tat delivered by AAV virus into BALB/cJ mice was not neurotoxic (Tang et al. Sci Rep. 2020 ;10(1):14002.). Our recent investigation combined exosomal Tat with a bispecific T-cell engaging (BiTE) molecule CD4-αCD3 which colocalizes the gp120 surface protein of HIV-1 and the CD3 of cytotoxic T lymphocytes. When latent HIV-1 is reactivated from resting CD4+ T cells with Exosomal Tat, cells with HIV-1 surface protein gp120 expressed on the cell membranes are targeted for immune cytolysis in the presence of CD4-αCD3. We’re performing ex vivo and in vivo experiments to test if this combination can reduce or eliminate HIV-1 reservoirs.