The past few years, Jim Dunn, a 74-year-old living with HIV in San Diego with his wife, Susan, has been struggling with serious skin cancers. Immunotherapy has been holding them at bay, but he acknowledges that his end of life may come faster than he previously thought.
And that’s why, about two years ago, he decided to participate in the Last Gift study at University of California-San Diego (UCSD). As part of Last Gift, people with HIV whose lives may end anywhere from as soon as six months or less to several more years agree to donate their bodies to HIV cure research. In addition to regularly donating blood and urine samples while still alive, those in the study agree that their bodies will be delivered for autopsy within hours of their death.
Dunn, a former Iowa management exec who retired to the San Diego area to be near his children, says that he already knew about the Last Gift study through his involvement with the UCSD HIV Community Advisory Board (CAB), which UCSD researchers consulted when designing the study. When he realized his cancers were serious, “I thought, ‘If push comes to shove, I don’t want my family to have to make those decisions for me that come at the end of life,’” he says, “so I decided to sign up for Last Gift.”
He continues: “If the worst happens to me, I want to be able to give this gift [of my body for research] to the HIV community. We stand on the shoulders of people before us who volunteered a lot for the research studies that went on.” He’s participated in five to six prior HIV-related studies, looking into such things as memory and aging in people living with HIV, so the enrollment experience was not new to him.
A Tough Study to Launch
The so-called “last gift” of HIV-positive people like Dunn could yield extraordinary discoveries about how HIV exists in the body, which in turn could yield breakthroughs including an HIV cure, according to UCSD’s Davey Smith, M.D., M.A.S., and Sara Gianella, M.D., who conceived of the study in 2016.
Researchers know that HIV hides in various parts of the body, “but we don’t know exactly where and how,” says Gianella, “and there is no way we can safely sample tissue [from various parts of the body like the brain] to find out in people who are alive,” she explains.
At the same time, she says, “Current autopsies were not designed for HIV cure research—the time between death and autopsy is too long, and reservoirs [of HIV] start degenerating.”
But designing and enacting a study that would enroll people at the end of life for a very quick autopsy once they died initially seemed like an impossible feat. “The first time [Smith] brought it up with me, it seemed crazy,” she says. “We would need to follow them closely [while still alive, via blood and urine samples right up until as close to death as possible], then do a rapid autopsy right after death. We’d also need to know exactly when the person took their last HIV med before death, which has an effect on if or when HIV would start replicating in someone’s body again.”
The first step was seeing if the San Diego HIV community would be on board with the idea. To do so, they created surveys that went out to people with HIV both with terminal disease and perfectly healthy. “The response was overwhelmingly positive,” says Gianella. “We were surprised by how open and excited people were to participating, seeing it as a historic opportunity.”
Once they started writing grant requests, reviewers at the National Institutes of Health (NIH) raised ethical questions, calling terminally ill patients “vulnerable,” which, in the rigorous ethical review process for studies, sets a very high bar for approval. “But the community pushed back and said, ‘No, we want this,’” says Gianella.
Jeff Taylor confirms that sentiment. Taylor is an HIV and cancer survivor in nearby Palm Springs, California, who directs the HIV + Aging Research Project and is a Last Gift study team member. “We told the study reviewers that, if anything, we’re less vulnerable because so many of us have already confronted our own death and have a more clear-eyed view of it, and because [as people living with HIV] we’ve often been excluded from research,” he says.
Working with renowned HIV research ethicist Karine Dubé, Dr.P.H., at the University of North Carolina, Smith and Gianella submitted a grant request to the NIH at least twice before it was approved.
Then there were the logistics, which involved finding someone available indefinitely 24-7 to transport a dead body immediately to the morgue for autopsy. In 2017, the study enrolled its first patient, Anthony Bennett, who was very public about his participation before his death that same year.
Since then, 27 people have enrolled in the study, grouped in two: those who will likely die in six months or sooner, and those who may live months or even years longer. (Most have various terminal cancers or end-stage organ failure.) Of the 27, 17 have died, and among those, 14 were autopsied. One enrolled patient was experiencing homelessness, and researchers did not learn of his death until it was too late; another went to the East Coast to die surrounded by family.
Last year, researchers published their first findings from the autopsies of six patients: mainly, and as expected, that HIV hides out throughout the body, including in the brain (although at very low levels in undetectable subjects), and that it moves across different bodily compartments, but more so in people with detectable virus on labs.
“Also,” says Gianella, “we noticed that the HIV reservoir expands within tissues [of different body parts]. When cells typically divide, they carry HIV with them, which is not the same thing as HIV replication. So if we want to cure HIV, maybe cell division is something we need to look at, even though the body needs it.”
There’s been no major a-ha moment yet, says Gianella, adding that they need to analyze more patients to look for patterns, “such as that maybe HIV tends to hide out most in one particular reservoir” of the body.
Study participation also comes with a perk of sorts: After autopsy, the study will pay for cremation, which ordinarily costs hundreds if not thousands of dollars.
Raising Existential Questions
Enrollment in the trial, which the researchers hope to expand to sites beyond San Diego to increase participation, is ongoing and occurs through outreach to local HIV community advisory boards and HIV providers. Participants so far are predominantly gay white men, with three cisgender women, one transgender woman, and two people of color. “I hope we can enroll a more diverse population going forward because we might see differences,” says Gianella.
One current participant, L., 73, who asked to remain anonymous because his family does not know his HIV status, was himself an HIV doctor who still works part time in medicine. He takes a medication for his arthritis that suppresses his immune system, which he feels makes him vulnerable to death, even though he says he currently has “functional health despite some frailty.” Like Dunn, he is in the “on-deck” group of participants who are not expected to die in six months or sooner.
He says he’s known Gianella and Smith for years via the local HIV community advisory board. The idea of the study shocked him at first—“I found it somewhat disrespectful”—but he says, with dry humor, that eventually he came around. “I have little faith in a cure for HIV, but why the hell not let Sara and Davey play with my tissue? I’m going to be dead, so I won’t know what’s going on anyway.”
But he doesn’t expect that to happen anytime soon. “I’m going to stay healthy until my four dogs die, so it’s going to be a while.”
One thing he is not sure of is if he would go off his HIV meds toward the assured end of his life—something, according to Gianella, that “we only ask [participants] to let us know if and when they decide to [do], but we never encourage or request it.” It comes with the chance that one might lose a final month or two of life.
“Some people on the advisory board said they’d be willing to do that, but I probably would not,” he says, “especially if my dogs are still alive, my cognition is good, and I’m having meaningful interactions with friends.”
Clearly, participation in the study raises tricky existential questions. No surprise, then, that participants can get close to the study operators—especially its community outreach coordinator, Susan Concha-Garcia, who has known some of the participants for years due to their involvement in other studies she supervised, or via the broader local LGBTQ community, of which she and her wife are a part. In fact, she knew Bennett and his spouse for 18 years before he entered the trial.
Participants have even asked her to be there when they die, she says. “I’m an older person who has seen a lot of things,” she says. “Sometimes they ask me to pray with them, because not all of them have a loved one with them at the end.” Most enrolled in Last Gift, she says, “because they wanted to give back to the community. They say, ‘I want this to be my legacy, my contribution. I want them to find a cure or a vaccine.’”
Taylor seconds that. “Our research found that the majority of people living with HIV were very in favor of this because they said it gives meaning to the end of life. It’s why we named the study Last Gift.”
Participants like Dunn and L. certainly feel that way. Says Dunn, “This is a way of giving back to the community that saved our lives.”
Learn more about the Last Gift study and contact researchers via their website.