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Despite extensive investigations, we still do not fully understand the dynamics of the total body HIV reservoir and how sub-reservoirs in various compartments relate to one another. Studies using macaque models are enlightening but eradication strategies will still need to be tested in humans. To take the next steps in understanding and eradicating HIV reservoirs throughout the body, we propose to develop a “peri-mortem translational research model” of HIV-infected individuals (called ‘The Last Gift’), which is similar to existing models in cancer research. In this model, altruistic, motivated HIV-infected individuals with advanced non-AIDS related diseases and with six months or less to live will participate in HIV cure research and donate their full body after they die. Engaging this population provides a unique opportunity to compare the HIV reservoir before and after death across multiple anatomic compartments in relation to antiretroviral therapy use and other relevant clinical factors. Furthermore, people living with HIV/AIDS at the end of their lives may be willing to participate to cure interventions and accept greater risks for research participation. A broad, frank, and pragmatic discussion about performing HIV cure research near the end of life is necessary.