Over the last decade, understanding human immunodeficiency virus’(HIV) persistence and developing strategies to cure HIV infections have emerged as key priorities for both the research community and people living with HIV (PLWH). It will be challenging to extinguish the global HIV epidemic through antiretroviral therapy (ART) alone; even among those with access to treatment, not all can sustain lifelong adherence to currently available regimens. Many of us working on strategies to reduce persistent immune activation despite ART—which may drive much of the accentuated age-related morbidity and mortality in this setting—also wonder whether these strategies can be fully effective without eradicating, controlling, or silencing the HIV reservoir. Thus, an HIV cure is an important goal. While the Berlin patient taught us that an HIV cure is possible [1], in the decade since his case was first reported, a number of obstacles to achieving this goal for the majority of PLWH have arisen. One of those obstacles is the persistence of HIV in tissue reservoirs that may be relatively more resistant to immune-mediated clearance and/or be exposed to lower antiretroviral drug concentrations. Indeed, the vast majority of persistently HIV-infected cells during ART reside in the gut, an immunoregulatory environment that may suppress immune-mediated clearance mechanisms, or in follicles within secondary lymphoid tissues that often exclude cytotoxic CD8+ T cells and natural killer cells [2]. Controversy also continues as to whether replication-competent HIV persists in myeloid-derived cells of the central nervous system during ART, which see far lower concentrations of antiretroviral drugs than plasma [3]. A major challenge to studying these important issues is the need for large amounts of tissue to fully characterize the burden and anatomic localization of infected cells, beyond what is typically feasible in biopsy procedures. Furthermore, some tissue sites, like the brain, are simply not safe to biopsy in otherwise healthy individuals. Postmortem tissues from autopsy procedures can often address these issues, but the time between death and autopsy/tissue preservation is typically too long to adequately preserve viable cells or HIV nucleic acids. Indeed, the postmortem degradation of tissues and nucleic acids begins almost immediately and impacts any scientific work conducted on posthumous tissue [4, 5], particularly the most advanced HIV RNA in situ hybridization (and sequencing with laser capture microscopy) techniques [6]. It is also often unclear whether a tissue donor interrupted ART for some period prior to death, complicating the interpretation of the presence of HIV RNA or proteins in tissues.

In this issue of Clinical Infectious Diseases, Sandstrom et al address these issues by describing a PLWH with a terminal illness that opted for medical assistance in death (MAiD). In the days prior to death, this incredibly generous participant elected to arrange for immediate posthumous tissue processing and donation of his remains to HIV research, so that his tissues could help address some of the barriers to tissue reservoir research described above. Tissues acquired post-MAiD (with preparation before death) theoretically provide the best opportunity to mitigate the effects of delayed tissue processing on the interpretation of downstream studies. We agree with the authors that tissues prepared as described may provide valuable insights for HIV cure research. Moreover, post-MAiD tissue donation offers a pathway for individuals with terminal illness to achieve the sense of fulfillment and purpose that can improve the patient experience at this final stage of life. Indeed, the authors …