How do people with HIV feel about volunteering for clinical trials testing experimental cures?
If their responses could be summed up in one phrase, it would be the quote that Laurie Sylla chose for the title of her recent talk on the topic: “We’re scared … and brave.”
Sylla is a member of the community advisory board for defeatHIV, based at Fred Hutchinson Cancer Research Center, one of six such research groups funded by the National Institutes of Health focused on curing the chronic viral infection.
Volunteer community advisory boards, known as CABs, serve as a bridge between researchers and the general public, making scientists aware of community concerns and translating complex, often jargon-filled concepts for non-scientists.
Sylla and other HIV cure advisory board members have taken their role one step further: They are doing research themselves, some of which they have been invited to present at international AIDS conferences.
“It’s kind of unusual for a CAB to do research,” she said. “’We’re usually advising the researchers. This is another way of making sure those [community] voices get heard.”
In spring 2016, she and board members advising HIV cure research groups in Los Angeles, San Francisco and Durham, North Carolina, held 10 focus groups around the country to ask how people with HIV felt about participating in HIV research. Monday night, she did what the advisory board believes all good researchers should do: She explained the findings from the Seattle groups to those who had participated in her project and other interested community members.
“A lot of people participate in research but don’t get to hear the results,” Sylla told the audience at Gay City: Seattle LGBTQ Center. “One of the things we promised at focus groups last spring was to report back.”
Community advisory boards were born in the early days of what would become a global pandemic that to date has killed about 35 million people. Rage, frustration and grief drove gay men — the community first hit by the then-mysterious disease dubbed AIDS — and their allies to storm scientific conferences. They demanded a voice in research decisions.
Today, community involvement is the norm in HIV research and a model for other disease advocates. And HIV is no longer the certain death sentence it was for the first 15 years of the pandemic. Antiretroviral drugs that stop HIV from replicating and causing harm, developed by 1996, are considered one of the great breakthroughs in modern medicine. Today, those who have access to and can tolerate the lifelong treatment can live a nearly normal lifespan.
But early hope that antiretroviral therapy, if taken long enough, would actually cure the viral infection did not pan out: Stop treatment, and HIV roars back like a kicked hornet’s nest. For many years, scientists all but gave up hope that a cure was possible.
That perception changed in 2008, when the world learned about Seattle-born Timothy Ray Brown. A year earlier, Brown had needed a bone marrow transplant to treat acute myeloid leukemia. In what proved to be a successful attempt to also cure Brown’s HIV infection, his doctor in Berlin — where Brown was living at the time — found a stem cell donor who carried two copies of a rare gene mutation that confers natural resistance to the virus.
This “proof of concept” that a cure was possible inspired scientists around the world to work on a variety of different — and less toxic — cure approaches.
But Sylla’s research on clinical trial participation uncovered a conundrum: For those not also facing a life-threatening cancer, is it worth it to take part in experimental cure research when you know you can control your disease through already-tested drugs?
For some people in the focus groups, the answer was yes, especially for those who became infected with HIV years or even decades ago and were experiencing a phenomenon familiar to those with chronic conditions: medication fatigue.
For others, Sylla said, the answer depended on the type of “cure” under consideration.
What makes an HIV cure so challenging is that the virus integrates itself into the DNA of some of the longest-lived cells in the body. These reservoirs of latent cells seed new infections if people stop taking their medication. A so-called “sterilizing” cure would eradicate every single bit of virus in every single one of these cells.
But most researchers believe that a “functional” cure would be more achievable, at least in the short term. By this they mean keeping the virus under control — so that it doesn’t do damage and can’t be transmitted — without the need for daily drugs. Scientists liken a functional cure to cancer remission. But as with cancer, it comes with uncertainties.
And uncertainties raise concerns. In addition to worries about possible side effects or risks from the procedure itself, focus group participants asked: Could they trust that a functional cure would be lasting? Would they go off their meds only to have the virus return? If so, how emotionally devastating might it be to think they were cured but find that they weren’t —a reasonable question, given the experience of one such patient in a recent study? If the virus returned, would it still respond to antiviral drugs or might it be harder to treat? How often would they have to be monitored to know whether the virus was really gone? Perhaps worst of all, could they inadvertently infect someone else if the virus returned and they didn’t know it?
“This is very different from the old days when people were participating in treatment trials because ‘I’m probably going to die if I don’t get this new thing,’” Sylla said. “Now people can live well without participating.”
Sylla was clear that these focus groups' concerns do not speak for all people with HIV. In addition, the findings she presented Monday were from four Seattle groups only — 31 people in total representing women, long-term survivors, Latino gay men and adults under age 30, respectively. (She and her co-researchers are writing up the results for publication based on data from all 10 focus groups across the country.)
Still, focus groups give the CABs — and the researchers they advise — insights into questions about cure research that need to be addressed so that people with HIV can make an informed decision about whether to take part.
“When we’re asking people to participate, we’re asking them, ‘Will you take a risk even when you have something that will probably manage your disease for a long time?’ It’s a different kind of ask. It’s complex,” she said.
Sylla “backed into” doing this kind of research, she said in an interview before Monday’s presentation. But her involvement with the HIV pandemic has been full-on since the very beginning.
With degrees in social welfare and human services administration, she was living in Albany, New York, in 1982 and running a community-based suicide hotline and drop-in center for the homeless. The U.S. Centers for Disease Control and Prevention had reported the first cases of a mysterious illness striking gay men the previous June, and the hotline started getting calls from gay men who were scared.
When the state health department decided to set up hotlines to address the growing crisis, Sylla wanted to be part of it. She was friends with a lot of gay men, so it felt personal. But she also was drawn to putting her skills to use where most needed.
“This was urgent. People were dying. Disenfranchised people were dying,” she said. “I believed I had the right skills to do what needed to be done, the community organizing and community education.”
First she was named to the planning task force for the new hotline. Then she was offered the job of running it, even though most of her friends told her it would probably go to a gay man, not a straight woman. She took it.
She thought she would do the job for a year, and then AIDS would be over.
Thirty-five years and a move to Seattle later, she’s still at it. Partly it’s a way of continuing the legacy of friends who had meant so much to her and who died in the epidemic.
It’s also because there is still work to do.
“We still haven’t addressed the basic inequities and injustice piece,” she said. “Yes, there’s treatment, but not everybody has access to treatment.”
Already she’s thinking of who will have access to future cures.
In her paid job, Sylla evaluates publicly funded mental health and substance abuse treatments for King County. But her passion for HIV remains. In 2013, when Timothy Ray Brown spoke at Fred Hutch for a panel on HIV cure research, Sylla was in the audience. DefeatHIV co-directors and Hutch researchers Drs. Hans-Peter Kiem, a transplant and gene therapy specialist, and Keith Jerome, a virologist, talked about using Brown’s case as a starting point to find a less harsh and more broadly applicable cure by genetically engineering resistance in an HIV-infected person’s own blood stem cells.
That was how Sylla came to join the defeatHIV CAB.
“I just thought it was the most brilliant thing I had ever heard,” she said. “I was more excited than I’d been in 30 years of doing HIV work.”
Funded again in 2016 for an additional five years, defeatHIV researchers are now working on using the immune system to eradicate or at least control HIV, in much the same way as immunotherapies are beginning to revolutionize cancer treatment. Kiem is continuing his work on cell and gene therapies. And Sylla is continuing to make sure potential volunteers understand the science behind a cure — and that researchers hear their concerns.
“Community-based participatory research is really where the future lies,” said defeatHIV CAB coordinator Michael Louella at an NIH conference in November.
Sylla presented her early findings to researchers at the annual defeatHIV-sponsored Conference on Cell and Gene Therapy for HIV Cure last August and will be presenting a new study at the International AIDS Conference in Paris in July.
The takeaway from her focus groups?
To be clear, people with HIV said they want a cure. Freedom from having to take medication, freedom from medication side effects, freedom from fear of infecting others, and — maybe most of all — freedom from the stigma which, 36 years into the epidemic, still surrounds the virus were among the reasons cited.
And many expressed a desire to participate in cure studies, even if they themselves would not benefit. “I would like to contribute to the possibility of a cure,” one focus group participant said. Others would do it as a way to “help the community move forward,” as a “way to give back,” as a way to help science and to be “part of history.”
But they also have needs: to better understand the science and the procedure. To grasp potential personal benefits — or lack thereof —and risks. They want researchers, clinicians, and others in the trial to take the time to understand them, not just as a research subject but as a person — their cultures, their languages, the stigma that they’ve faced, and the trauma they’ve lived through after learning they had HIV. And they want those conducting the trial to be there for them if anything goes wrong.
“They want to feel like they’re contributing to the greater body of knowledge,” Sylla said. “But they want to feel like they can trust you like they’re being treated with respect. It is scary to participate in the trial of something brand new. Researchers need to understand that people are both scared and brave at the same time.”
Join the conversation on our Facebook page.
Mary Engel is a former staff writer at Fred Hutchinson Cancer Research Center. Previously, she covered medicine and health policy for the Los Angeles Times, where she was part of a team that won a Pulitzer Prize for Public Service. She was also a fellow at the Knight Science Journalism Program at MIT. Follow her on Twitter @Engel140.